review article propolis: a complex natural product with a ... · bee glue, is a natural ......

Review ArticlePropolis A Complex Natural Product witha Plethora of Biological Activities That Can BeExplored for Drug Development

Ricardo Silva-Carvalho12 Faacutetima Baltazar12 and Cristina Almeida-Aguiar3

1Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho 4710-057 Braga Portugal2ICVS3Brsquos PT Government Associate Laboratory Guimaraes 4710-057 Braga Portugal3Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) Biology DepartmentUniversity of Minho 4710-057 Braga Portugal

Correspondence should be addressed to Cristina Almeida-Aguiar cristinaaguiarbiouminhopt

Received 25 February 2015 Revised 10 May 2015 Accepted 12 May 2015

Academic Editor Jairo Kennup Bastos

Copyright copy 2015 Ricardo Silva-Carvalho et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The health industry has always used natural products as a rich promising and alternative source of drugs that are used in the healthsystem Propolis a natural resinous product known for centuries is a complex product obtained by honey bees from substancescollected from parts of different plants buds and exudates in different geographic areas Propolis has been attracting scientificattention since it has many biological and pharmacological properties which are related to its chemical composition Several invitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolatedcompounds as well as to evaluate and validate its potential Yet there is a lack of information concerning clinical effectivenessThegoal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerningthe chemical composition and the biological properties of this natural compound from different geographic origins

1 Introduction

Over the years nature is continually surprising with diver-sified natural compounds that can be promising sources forthe discovery of new drugs important in medicine [1] Infact approximately half of the currently available drugs wereobtained from natural compounds or related [2] The use ofnatural products as an essential route to new pharmaceuticalleads is continually growing and is a research field of enor-mous interest because the different structural range of naturalcompounds can provide lead compounds for therapeuticimprovement based on rationalized molecular modifications[3 4] It is well known that scientists have curiosity in herbsand other natural plant products for research however onlyin the last years the interest in modified plant productsby animals which normally have been largely ignored andwasted has been increased [5 6]

Propolis a complex mixture of compounds also calledbee glue is a natural resinous product that honeybees collectfrom several plants and mix it with beeswax and salivaryenzymes (120573-glucosidase) [7ndash11] As inferred for the meaningof the Greek word propolismdashpro- for or in defence andpolis the city [10]mdashbees use propolis on their hives asprotection against predators and microorganisms to repairdamage as a thermal isolator and to build aseptic localsto prevent microbial infection of larvae [7 9 10 12] Sinceancient times propolis has been used by humans to meetthe needs of health and food preservation [5] but only inthe last years the interest in this complex natural producthas increased due to its broad spectrum of biological andpharmacological properties [12ndash14] Propolis is a lipophilicmaterial that is hard and breakable when cold but softflexible and very sticky when warm it possesses an enjoyablearomatic smell and different coloration including brown

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 206439 29 pageshttpdxdoiorg1011552015206439

2 Evidence-Based Complementary and Alternative Medicine

green and red among others [5 7 12] In terms of chemicalcomposition it is generally composed of 50 resin 30wax 10 essential oils 5 pollen and 5 other substanceswhich includeminerals and organic compounds like phenolicacids (cinnamic and caffeic acid) or their esters flavonoids(flavones flavanones flavonols and dihydroflavonols chal-cones) terpenes aromatic aldehydes and alcohols fatty acidsstilbenes and 120573-steroids [8 9] Analysis of different samplesrevealed that propolis chemical composition is difficult tostandardize because it depends on different phytogeographiccharacteristics like vegetation season and environmentalconditions of the site of collection as bees select differentplants in different habitats for propolis production [6 8 9]

Several in vitro and in vivo studies have been describingthe plethora of biological activities and chemical profilesof propolis from different geographic origins This reviewhighlights published data about such works focusing on theantimicrobial anti-inflammatory antioxidant immunomod-ulatory and antitumor activities of different propolis types inorder to unravel the potential of this natural compound forthe development of new drugs

2 Use of Propolis in Ancientand Current Times

Propolis is not a new discovery Since beersquos domesticationmen explore its products to their own benefit and propolisone of the most important chemical weapons of bees is noexception having been employed extensively since almostimmemorial times [6 13 15ndash17] It is stated that propolis usedates back to ancient times at least to 300 BC where it wasused in folk medicine and other activities in many parts ofthe world [16] It was familiar to the Egyptians in particularby the priests who controlled medicine and chemistry andknew very well propolis antiputrefactive properties Theylearned from the bees the embalming capacity of propolis asthis natural product is used to perform the mummificationof corpses and prevent spread of infections The Greekand the Roman physicians also acknowledged the potentialof propolis by employing it in wound treatment as anantiseptic and cicatrizing agent and as mouth disinfectantThe Persians described propolis as a drug capable of actingagainst eczemas myalgia and rheumatism Populations ofthe new world like Incas also used propolis as an antipyreticagent

Between the 17th and 20th century this natural productbecame very popular in Europe In 1969 in the former Unionof Soviet Socialist Republics (USSR) the use of propolis wasaccepted in human and veterinary medicine with severalapplications including the treatment of tuberculosis wherethe regression of lung problems and recovery of appetitewere observed Also it was believed to cure some diseases infolk Georgian medicine During World War II (1939ndash1945)doctors used propolis to treat wounds [15ndash17] but only in1985 in Japan propolis was considered as very promising inpharmacology Before that propolis was considered a prod-uct without market value especially because its productionis low and affects honey production Nowadays propolisis an important product in alternative medicine in Japan

being widely imported from Brazil [18] In the 17th centurythe Italian Antonio Stradivari who is considered the mostsignificant and the greatest crafter of string instruments likeviolins used propolis as an ingredient in the varnish of hisinstruments Curiously such as in the 17th century propolisis currently used in rosin for stringed instruments and in therepair of accordions [16]

Propolis is one of the few natural products that main-tained popularity for a long time although it is not considereda therapeutic agent in conventional medicine Actually it iswidely used as a component in pharmaceutical and cosmeticproducts such as antiacne creams facial and body creamsointments and lotions and several formulations for oralhygiene [15 16] It is also used in some foods and beveragesor simply as food supplement or healthy drinks This namewas attributed to the drinks because it is thought that propolisimproves human health and prevents diseases such as heartdisease or diabetes among others [19]

3 Origin and Composition of Propolis

Propolis knowledge has registered an important evolutionover time due to exhaustive studies regarding its chem-ical composition and biological activities In the 60s itwas thought that despite its complexity propolis chemicalcomposition was more or less constant Nevertheless inthe following years analysis of a large number of samplesfrom different geographic origins revealed that chemicalcomposition of propolis is highly variable and also difficultto standardize because it depends on factors such as thevegetation season and environmental conditions of the siteof collection [6 8 9] Marcucci [7] and Bankova et al [10]registered more than 300 substances in propolis and recentreports showed the presence of compounds never mentionedbefore [12 17 20 21]

Generally the main constituents of propolis are resin andvolatiles which are substances obtained from a variety ofbotanical processes in different parts of plants and beeswaxsecreted by the bees [9] Typical compounds are summarizedin Table 1 As can be seen plant sources vary among thedifferent parts of the globe leading to panoply of compoundsIn a review on propolis standardization different resin typeswere proposed poplar propolis birch green red ldquoPacificrdquoand ldquoCanarianrdquo [9 12] Samples of poplar propolis (egfrom Europe North America New Zealand and temperatezones of Asia) are mainly composed of flavonoids phenolicacids and their esters [10 20 22] clearly different fromother propolis types (Table 1) Portuguese propolis despitesimilar to the ones found in European samples also containsnew methylated esterified and hydroxylated derivatives offlavonoids and pinocembrinpinobanksin derivatives con-taining a phenylpropanoic acid derivative moiety in theirstructure [20 21] Our group recently showed that propolisfrom Pereiro (district of Guarda Beira Alta) (Figure 1) has ahigh concentration of phenolic components [23]

Poplar-type propolis is undoubtedly themost studied onebut there are many other propolis types Recent studies haverevealed a new type of European propolis Mediterraneanpropolis This type of propolis is distinguished by the high

Evidence-Based Complementary and Alternative Medicine 3

Figure 1 Crude sample of propolis from Pereiro obtained in thecentral region of Portugal (Guarda)The sample was kindly suppliedby Engineer Pedro Fernandes (Mel do Abel)

concentration of diterpenoids and is found in many regionslike Greece [24 25] Switzerland [26]Malta [27] Turkey [28ndash30] or Algeria [28 31]

Propolis from tropic regions like Brazil CubaVenezuelaand Chile has been attracting much attention in thelast years due to its particular chemical profiles Preny-lated phenylpropanoids prenylated p-coumaric acids ace-tophenones diterpenic acids and caffeoylquinic acids wereshown to be very common and abundant in propolis fromBrazil mainly from the south-eastern region [9 10 21]The flavonoids kaempferide and isosakuranetin and someamounts of kaempferol were also found in Brazilian samples[32] Additionally red propolis from the northeast regionsof Brazil presents high concentrations of phenolic acids andthe flavonoids formononetin isoliquiritigenin liquiritigeninmedicarpin and biochanin A [33ndash35] Cuban propolis hasa peculiar enrichment in polyisoprenylated benzophenonesmore specifically nemorosone and a minor content of amixture of xanthochymol and guttiferone E [9 36] makingthis type of sample chemically distinct from both Europeanand Brazilian propolis Propolis from Venezuela is alsocomposed of polyisoprenylated benzophenones in additionto the usual constituents found in samples of tropical regions[9 37 38]

Information about the chemical composition of Aus-tralian propolis is very limited despite the great biodiversityof the island Propolis from Kangaroo Island is mainlycomposed of stilbenes some of them being prenylated Ad-ditionally it has also some prenylated cinnamic acids andflavonoids [39] like 210158403101584041015840-trimethoxychalcone 21015840-hy-droxy-3101584041015840-dimethoxychalcone 2101584041015840-dihydroxy-31015840-metho-xychalcone 57-dihydroxy-23-dihydroflavonol 3-acetate (pi-nobanksin 3-acetate) and 57-dihydroxy-6-methoxy-23-dihydroflavonol 3-acetate [40] Western Australian propolisis composed of Xanthorrhoeol pterostilbene sakuranetinand pinostrobin [41] Propolis of Australian stingless bees(Tetragonula carbonaria) is composed of C-methylatedflavanones [42]

ldquoPacificrdquo propolis (eg Okinawa Taiwan Hawaii Indo-nesia and Myanmar) is another particular type of propolisA new family of compounds the prenylflavonoids morespecifically isonymphaeol-B was identified in Okinawapropolis although three already known compoundsmdashnym-phaeol-A nymphaeol-B and nymphaeol-Cmdashhave also

been isolated in three samples [43] As Okinawan propolisHawaiian propolis is also composed of nine prenylflavonoids[44] Taiwanese propolis is composed of eight prenylfla-vanones nymphaeol-A nymphaeol-B and nymphaeol-Cpropolins A B and E isonymphaeol B and 31015840-geranyl-naringenin [45] In another sample of the Pacific regionthe Indonesian propolis an inseparable mixture of fouralk(en)ylresorcinols (5-pentadecylresorcinol 5-(81015840Z111015840Z-heptadecadienyl)-resorcinol 5-(111015840Z-heptadecenyl)-resor-cinol and 5-heptadecylresorcinol) along with four prenylfla-vanones propolins D C F and G and three cycloartane-type triterpenes mangiferolic acid isomangiferolic acidand 27-hydroxyisomangiferolic acid was identified [46]Additionally fractioning of propolis extracts from Myanmarled to the isolation of two new cycloartane-type triterpenestogether with 13 cycloartanes and four known prenylatedflavanones [47] Thailand propolis which might bepossibly obtained from Styrax trees comprises not onlythe typical compounds of temperate regions but also thetwo new phenylallylflavanones (710158401015840S)-8-[1-(41015840-hydroxy-31015840-methoxyphenyl)prop-2-en-1-yl]-(2S)-pinocembrin and (E)-cinnamyl-(E)-cinnamylidenate [48] In propolis fromCanaryIslands a different phenolic profile was found furofuranlignans being the main compounds Six furofuran lignanswere isolated and characterized as sesamin episesaminmethyl xanthoxylol aschantin sesartenin and yangambinPropolis also contains sugars and sugar alcohols [10 49]Many studies with African propolis from different regionslike Kenya Cameroon Congo Oman and Ethiopia showedthat triterpenoids are major chemical components [50ndash53]Southern Nigeria propolis is uncommon since it presentsprenylated isoflavonoids like Brazilian red propolis and ahigh abundance of stilbenoid compounds [54]

Propolis additionally contains minerals such as mag-nesium calcium iodine potassium sodium copper zincmanganese and iron some vitamins like B1 B2 B6 CE and D as well as provitamin A a few fatty acids andalso some enzymes derived from bee glandular secretion orpossibly from pollen like succinic dehydrogenase adenosinetriphosphatase glucose-6-phosphatase acid phosphatase120572-amylase 120573-amylase 120572-lactamase 120573-lactamase maltaseesterase and transhydrogenase [17 55] Polysaccharides likestarch and the di- and monosaccharaides glucose fructoseribose rhamnose talose gulose and saccharose are com-monly present in propolis too [55]

4 Biological Properties and TherapeuticActivity of Propolis

Despite propolis popularity over time it is not consid-ered as a therapeutic agent in conventional medicine asthe standardization of chemical composition and biologicalactivity is lacking Such standardization is indispensablefor acceptance in the health system Thus characterizationof different types of propolis according to its plant originand corresponding chemical profile is mandatory Studiesabout propolis bioactivity must start with chemical profilingof the extracts since that information is essential to havedetailed and consistent comparative data between each type


Table1Ch

aracteris

ticcompo

unds

ofprop

olisfro

mdifferent

geograph

icoriginsa

ndrespectiv

eplant

source

Geographico

rigin

Plantsou

rce

Typicalcon

stituents(m

aincompo

nents)

References

EuropeN

orth

AmericaNew

Zealandand

temperatezoneso

fAsia

Popu

lusspp

morep

redo

minantly

Pnigra

Pino

cembrinpinob

anksinchrysingalangin

caffeicacidferulicacidcinnamicacidand

their

esters

[102022]

Brazil

Green

prop

olis

Baccharis

spppredo

minantly

Bdracun

culifolia

Prenylated

phenylprop

anoidspheno

licacidsprenylated

p-coum

aricacidsacetop

heno

nes

diterpenicacidscaffeoylquinica

cidskaempferideiso

saku

ranetin

and

kaem

pferol

[9103233]

Redprop

olis

Dalbergiaecastaphyllum

Form

onon

etinisoliq

uiritigeninliquiritigeninm

edicarpin

andbiochaninA

[323435]

Russia

Betulasppm

ores

pecificallyB

verrucosaB

pend

ulaandB

pubescens

Cinn

amicacidsph

enylprop

anoidsesquiterpenolsacacetinapigenin

ermaninrhamno

citrin

kaem

pferide120572-acetoxybetuleno

l[10180]

CubaV

enezuela

Clusiasppm

ores

pecificallyC

rosea

andC

minor

Polyiso

prenylated

benzop

heno

nesmores

pecificallynemoroson

exantho

chym

oland

guttiferone

E[936]

Mediterranean

Greece

Prob

ablyCo

nifer

spp

Flavon

oidsditerpenicacidssuchas

isocupressic

pim

aricand

commun

icacidsiso

agatho

lal

agathadiolferrugino

l8-elem

eneandtotarol

[2425]

Switzerland

Ptre

mula

Benzylp-coum

aratebenzylferulateandph

enolicglycerides

liked

icou

maroylacetylglycerol

diferuloylacetylglycerolferuloylcou

maroylacetylglycerolandcaffeoylcou


[26]

Malta

Ferulaspp m

ostp

robablyFerula

commun

isDiterpenicacidssuchas

isocupressic

com

mun

icpim

aricand

imbricatoloica

cidtogether

with

totaroland

13-epitorulosal

[27]

Turkey

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativa

Pino

cembrinpinob

anksin

andits

acetateprenylestersof

caffeicacidferulicacidsditerpenicacids

likep

imaricisopimaricabieticdihydroabietic

acidscinn

amylcinn

amateandethyloleate

arom

aticacid

esterssuch

asbenzylcinn

amatebenzenedicarbo

xylic

acid

andflavano

lssuch

asbenzop

yran

andchrysin

[28ndash30]

Algeria

Popu

lusspp

Cistu

sspp

Pino

cembrinpinob

anksin

andits

acetatechrysin

apigenin

pectolinarigeninpilo

sinladanein

galang

inn

aringenin

tectochrysinm

etho

xychrysin

prenyleste

rsof

caffeicacidsferulic

acids

diterpenicacidslikeh

ydroxyditerpenicacidlabdaneand

clerod

ane

[2831]

Austr

alia

Apismellifera

Acaciaparadoxa

Xantho

rrho

eolpterostilbenesakuranetinpinostro

bin

stilbenesprenylatedtetrahydroxystilbenes

prenylated

cinn

amicacidsflavano

nesflavono

lschalcones

[39ndash

42181]

Stinglessb

eeTetra

gonu

lacarbonaria

Ctorellianatre

es(fr

uitresins)

Africa

Nigeria

Prob

ablyMschwe

infurthii

Isofl

avon

oidsprenylatediso

flavono

idsandstilbenoids

[54]

Kenya

Triterpenesarylnaphtalenelignans

such

astetrahydrojusticidinBand6-metho

xydiph

yllin

geranyl

stilbenesand

geranylflavon

macarangin

[50]

Cameroo

nCon

goTriterpenesderivatives

ofam

yrin

andlupeolanddiprenylflavono

ids

[53]

Oman

Azadira

chta

indicaA

cacia

sppand

Mangifer

aindica

Triterpenesprenylatedflavano

nessuchas

7-O-m

ethyl-8

-prenylnaringenin

310158408-diprenylnaringenin

and8-prenyl-57-dihydroxy-31015840-(3-hydroxy-3-methylbutyl)-41015840-m

etho

xyflavano

nechalco

nes

cardanolcardo

lsandanacardica

cids

[51]

Ethiop

iaProb

ablyAc

aciaspp

Triterpenoids

such

as120572-a

nd120573-amyrins120572-a

nd120573-amyrylacetateslup

eoland120572-a

nd120573-lu

peyl

acetates

[52]

Thailand

Styrax

trees

Phenylallylflavanon

e(E)-cinn

amyl-(E)-cinnamylidenate

[48]

TheP

acificr

egion

OkinawaHaw

aiiandTaiwan

Macaranga

tanariu

sPrenylflavono

idsmores

pecificallyiso

nymph

aeol-Bnym

phaeol-Anym

phaeol-Bnym

phaeol-C

prop

olins31015840-geranyl-naringenin

[43ndash45]

Indo

nesia

Myanm

arMangifer

aindica

Alk(en)ylresorcinolscyclo

artane-ty

petriterpenescycloartanesandprenylated

flavano

nes

[4647]

Canary

Island

sUn

know

nFu

rofuranlignans

[49182]


of biological activity and chemical data This informationallows extrapolating the possible activity and mechanism ofaction of new propolis under study and provides substantialclues for the development of new drug candidates [6 9]

In the last decades several studies have demonstrated thebiological and pharmacological actions of different world-wide propolis samplesThe following sections summarize therecent published information about antibacterial and anti-fungal [6 7 56ndash59] antiviral [7 59 60] anti-inflammatory[61] antioxidant [62ndash64] immunomodulatory [6 65 66]and antitumor activities [8 17 23 64 66 67] revealing theinterest of researchers in this bee product and its potentialfor the development of new drugs as well

41 Antioxidant Activity It is well known that an endogenousstimuli like cellular metabolism and exogenous agents likeUV toxins and drugs among others generate reactiveoxygen species (ROS) such as hydrogen peroxide (H

2O2) the

superoxide anion (O2minus) and hydroxyl ion (HOminus) as well as

reactive nitrogen species (RNS) especially nitric oxide (NO)Carbohydrates proteins lipids and nucleic acids amongother biomolecules when exposed to the reactive speciessuffer oxidative modifications that modify the cell and leadto its death [68ndash70] Oxidative stress is responsible for theoccurrence of a wide variety of human diseases such asneurodegenerative [71] or cardiovascular diseases [72 73]cancer [68 74] diabetes [6] and atherosclerosis [75]

In the last years several studies have been performedto evaluate the antioxidant capacity of natural productsPropolis extracts composed of different polyphenols havebeen reported to possess a potent antioxidant activity [7076 77] Additionally the chemical varieties in differentpropolis samples from different regions have an influenceon the antioxidant activity Recently Fabris et al showedthat a sample of Italian and Russian propolis ethanol extract(PEE) which have a similar polyphenolic composition havea similar antioxidant activity while Brazilian PEE whichhave low polyphenolic composition have a weak antioxidantactivity [78] Another study also showed using differentsamples of Transylvania PEE a positive correlation betweenhigh polyphenolic composition and high antioxidant activity[79] Phenolic acids and flavonoids are characterized bya powerful antioxidant activity which is closely related tothe chemical structure of the compounds [80] Briefly theantioxidant activity is exerted by inhibiting the activity ofsome enzymes (eg xanthine oxidase protein kinase Cascorbic acid oxidase cyclooxygenase lipoxygenase Na+K+ATPase and cAMP phosphodiesterase) which inhibit theproduction of ROS species by scavenging interrupting thereactions that lead to the lipid peroxidation by chelatingmetal ions mainly iron and copper that are involved in theprocess of free radical creation or by potentiating the actionof other antioxidants [55] Table 2 summarizes some of thestudies addressing the antioxidant activity of propolis

Moreira et al [62] and Miguel et al [63] proposed thatPortuguese propolis an important source of total phenolsflavones and flavonols could be beneficial for human healthdue to its antioxidant properties Portuguese propolis alsoprotects human erythrocytes from free radicals damaging

by decreasing lipid peroxidation [64] These studies suggestthat Portuguese propolis is a powerful antioxidant agentthat can be used against oxidative stress thus maintainingthe structural and functional integrity of the cells Cuesta-Rubio et al [36] demonstrated that nemorosone the mostabundant polyisoprenylated benzophenone present in Cubanpropolis exhibits antioxidant capacity However when thiscompound suffers methylation a process that facilitates theseparation of the compound from the propolis sample theantioxidant property is abolished Ethyl acetate extract ofKangaroo Island propolis which is rich in stilbenes showeda stronger scavenging activity [39] Yang et al showed thatethyl acetate of propolis collected in Anhui China hasstrong scavenging activity and ferric reducing activity thoseactivities being influenced by caffeic acid phenethyl caffeatecinnamyl caffeate and benzyl caffeate [81] Another studyshowed that samples of methanolic extracts of Algerianpropolis that contains high amounts of caffeic acid estersand flavanones kaempferol and galangin possess strongscavenging activity and ferric reducing activity [31] Uruguaypropolis with high polyphenolic composition inhibits low-density lipoprotein (LDL) peroxidation and protein nitra-tion in vitro Moreover it induces the expression of nitricoxide synthase (eNOS) and inhibits NADPH oxidase inbovine aortic endothelial cells [82] In another study thetopical administration of Romanian PEE in mouse eitherprior to or after UVB exposure significantly attenuated themalondialdehyde (MDA) formation and restored glutathioneperoxidase (GSH-Px) activity [83] Talas et al [84] showedthat Turkish PEE has antioxidant properties in the livertissue of NOS inhibited rats In fact NOS inhibition causedan increase in CAT activity and MDA levels effect thatwas significantly decreased when the rats were treated withPEE It is well known that propolis composition is variablenevertheless one of itsmajor components CAPE (caffeic acidphenethyl ester) plays an important role in the antioxidantactivity [85ndash87]

Antioxidant activity is one of the most studied andimportant activities of propolis though there are no studieswith data on the safe dose to be used in humansThus clinicalstudies using propolis and its active compounds are needed

42 Anti-Inflammatory Activity Inflammation is an eventthat normally occurs in response to the constant exposureto environmental and endogenous stimuli as well as toaccidental damage [61] A complex cascade of chemicalsignals initiates after tissue injury and maintains a hostresponse to repair the injured tissue There are two stagesof inflammation acute and chronic Acute inflammation ismediated through the activation of the immune system cellswhich migrate to the site of damage and release growthfactors cytokines and ROSRNS species Chronic inflamma-tion occurs when the acute inflammation is not successfullyresolved This inflammatory condition plays a critical role inthe pathogenesis of many diseases including atherosclerosiscancer asthma Alzheimerrsquos and Parkinsonism [88 89]

Several studies have associated different types of propolisand its various constituents with anti-inflammatory activ-ity [61 90ndash95] Table 3 summarizes the anti-inflammatory


Table2Antioxidant

activ

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Portug

al(Serra

deBo

rnes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Hum

anerythrocytes

Decreaseinlip

idperoxidatio

n[64]

Free

radicalscaveng

ing

[62]

Brazil

Prop

olisfro

mthes

tinglessb

eeMelipona

orbignyi

prob

ablypo

plar

tree

PEE

Hum

anerythrocytes

Free

radicalscaveng

inginhibitio

nof

hemolysisandlip

idperoxidatio

n[183]

Portugal(C

entral

Algarve)

European

prop

olisPopu

lus

nigra

PEE

PWE

andmethano

licextracts

Free

radicalsscavenging

chelatio

nof

metalions

[63]

Cuba

Redprop

olisC

rosea

Methano

licextract

Nem

oroson

eFree

radicalsscavenging

[36]

Slovenia

European

prop

olisPopu

lus

nigra

PEE

Strong

redu

cing

power

andabilityto

scavenge

freer

adicals

andmetalions

[184]

Romania

European

prop

olisPopu

lus

nigra

PEE

FemaleS

wiss

mice(UVB

expo

sure)

Decreaseinmalon

dialdehyde

levels

resto

ratio

nof

glutathion

eperoxidase

activ

ity[83]

Kang

aroo

Island

Austr

alianprop

olisAc

acia

paradoxa

Ethylacetateextractstilbenes

Free

radicalscaveng

ing

[39]

China

European

prop

olisPopu

lus

nigra

Ethylacetateextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[81]

Algeria

Mediterranean

prop

olisPopu

lusspp

andCistu

sspp

Methano

licextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[31]

Urugu

ayEu

ropean

andgreen

prop

olisPopu

lusn

igra

andB

dracun

culifolia

PEE

Bovine

aorticendo

thelialcells

Inhibitio

nof

low-densitylip

oprotein

peroxidatio

nand

NADPH

oxidasea

ndincrease

innitricoxides

ynthase

[82]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

C57B

L6mice(acutelun

ginflammationcaused

bycigarette

smoke)

Normalizationof

nitritem

yeloperoxidase

levels

superoxide

dism

utasecatalaseand

glutathion

eperoxidasea

ctivity

and

redu

ctionof

glutathion

eoxidized

glutathion

eratio

and

malon

dialdehyde

levels

[185]

Turkey

Mediterranean

prop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

nea

sativa

PEE

Fibrob

lastcells

Decreaseo

fDNAdamageind

uced

byH

2O2

[186]

MaleW

istar

rats

DecreaseinCA

Tactiv

ityandMDAlevelsin

NOSinhibited

rats

[84]

Carps

(Cyprin

uscarpio)

Decreaseinmalon

dialdehyde

levels

superoxide

dism

utase

activ

ityandincrease

ofcatalase

andglutathion

eperoxidase

activ

ity[187]

Purchasedfro

mSigm

aAldric

hCo

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Free

radicalscaveng

inginhibitio

nof

xanthine

oxidasea

ctivity

andlip

idperoxidatio

n[85]

MaleW

istar

albino

rats

Maintenance

ofsuperoxide

dism

utasea

ctivitydecreaseo

fxanthine

oxidasea

ctivity

andmalon

dialdehyde

andnitric

oxidaselevels

[86]

Perip

heralblood

mon

onuclear

cells

from

cyclists

Redu

ctionof

hypertherm

ia-in

ducedsurvivalinhibitio

nnecrosis

superoxide

prod

uctio

nglutathion

edepletio

nand

intracellularsup

eroxide

[87]


Table3Anti-infl

ammatorymechanism

sinvestig

ated

with

prop

olis

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

PurchasedSigm

aAldric

hCo

Synthesiz

ed

Characteristic

ofEu

ropeanB

razilian

andMediterraneanprop

olis

Caffeicacidquercetin

narin

genin

CAPE

Periton

ealm

acroph

ages

Supp

ressionof

lipoxygenasep

athw

ayof

arachido

nica

cid

metabolism

CAPE

beingthem

ostp

otentm

odulator

ofthea

rachidon

icacid

cascade

[90]

Croatia

European

prop

olisPopu

lusn

igra

Water-solub

lederiv

atives

Swiss

albino

mice

Redu

ctionof

DNAdamageinperip

herallym

phocytes

[188]

PEE

MaleS

wiss

albino

mice

Supp

ressionof

functio

nalactivity

ofmacroph

ages

[104]

PurchasedSigm

aAldric

hCo

J774

macroph

agesM

ale

Wistar

rats

Invitro

andin

vivo

inhibitio

nof

cyclo

oxygenase1

and

cyclo

oxygenase2

activ

ity[91189]

MaleW

istar

albino

rats

Decreaseo

fpolym

orph

onuclear

neutroph

ilicleuko

cyte

infiltra

tionin

thelun

gstissues

[190]

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Gastricepith

elialcelllin

e(A

GS)H

pylori(str

ainNCT

C116

38)

Inhibitio

nof

Hpylori-ind

uced

NF-kB

andactiv

ator

protein

1-DNA-

bind

ingactiv

itypreventionof

IkB120572

degradationin

AGSandsupp

ressionof

TNF-120572andinterle

ukin

8prod

uctio

n[191]

PurchasedWakoPu

reCh

emicalIndu

stries

Ltd

RAW2647macroph

ages

Decreaseo

fthe

prod

uctio

nof

interle

ukin-1120573m

onocyte

chem

oattractant

protein1andthep

rodu

ctionandexpressio

nof

tumor

necrosisfactor120572(TNF-120572)

[98]

MaleS

wiss

inbred

strainmice

Decreaseo

fcyclooxygenase2

expressio

nNF-120581Bactiv

ity

c-Jun-N-te

rminalkinaseinh

ibito

rofN

F-120581Bkinase

(IKK

)andinhibitoro

fNF-120581B(IkB

)pho

spho

rylatio

n[97]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

RAW2647macroph

ages

Dow

nregulationof

NF-120581B

p38mito

gen-activ

ated

protein

kinaseand

c-Jun-N-te

rminalkinase

[101]

PurchasedAc

ros

Organics

Characteristic

ofEu

ropeanB

razilian


olis

Caffeicacid

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Sprague-Daw

leyrats

Inhibitio

nof

carrageenan-indu

cedrath

indpawse

demaa

ndthec

hemotaxisof

human

polymorph

onuclear

leuk

ocytes

(PMNs)

[95]

Synthesiz

edCh

aracteristic

ofEu

ropean

type

prop

olis

CAPE

Polymorph

onuclear

leuk

ocytes

obtained

from

Hum

anbloo

dInhibitio

nof

5-lip

oxygenasea

ctivity

andarachido

nica

cid

release

[103]

Chile

European

prop

olispo

plar

trees

PEE

MaleC

F-1m

ice

Inhibitio

nof

NOreleaseb

ythem

acroph

ages

[102]

China

European

prop

olisPopu

lusn

igra

PEEandPW

EMaleICR

micea

ndmale

Wistar

rats

Inhibitio

nof

thea

ctivationanddifferentiatio

nof

mon

onuclear

macroph

agesdecreasep

rosta

glandin-E2

(PGE2)

andnitric

oxide(NO)levels

[61]

Brazil

Green

prop

olisB

dracun

culifolia

PWE

Swiss

andBA

LBcmice

Decreaseinthen

umbero

fmacroph

ages

andneutroph

ils

inhibitio

nof

proinfl

ammatorycytokinesa

ndincrease

ofanti-inflammatorycytokines

[99]

Redprop

olisDalbergia

ecastaphyllum

PEE

MaleW

istar

rats

Decreaseinrenalm

acroph

ageinfi

ltrationin

ratswith

chronic

kidn

eydisease

[100]

Nepal

Nepalesep

ropo

lisprobablyShorea

robu

staD

albergiasissooAc

acia

catechuandBo

mbaxcie

ba

PEE

3101584041015840-dihydroxy-4-

metho

xydalbergion

e4-etho

xydalbergion

cearoin

andchrysin

Bone

marrow-derived

mast

cells

(BMMC)

from

C57B

L6

mice

Inhibitin

gIL-6T

NF-120572and

IL-13gene

expressio

nin

BMMC

andalso

inhibitin

gthea

ctivationof

IKKleadingto

NF-120581B

inactiv

ation

[96]


mechanisms investigated with propolis and its chemicalconstituents Recently the role of the flavonoids quercetinflavonols and flavones in modulating inflammatory cellfunction was studied [92] Funakoshi-Tago et al [96] inves-tigated the anti-inflammatory effects of flavonoids isolatedfrom Nepalese PEE on the IL-33 signaling pathway Theisolated flavonoids 3101584041015840-dihydroxy-4-methoxydalbergione4-methoxydalbergion cearoin and chrysin inhibited theexpression of inflammatory genes including IL-6 TNF-120572and IL-13 in bone marrow-derived mast cells (BMMC) andalso inhibited the activation of IKK which leads to thedegradation of I120581B120572 and inhibits the activation of nuclearfactor 120581B (NF-120581B)

The release and oxygenation of arachidonic acid are acritical event in inflammation Mirzoeva and Calder [90]demonstrated that propolis components such as CAPE caf-feic acid quercetin andnaringenin among others inhibit theproduction of eicosanoids In fact these components signif-icantly suppressed the lipoxygenase pathway of arachidonicacid metabolism CAPE being the most potent modulatorAnother study indicated that CAPE treatment improveshepatic steatosis induced by high-fat diet in a mouse modelThis effect was attributed to the reduction of c-Jun-N-terminal kinase (JNK12) andNF-120581B activationwith decreasein COX-2 expression [97] Recently it was reported thatCAPE exhibits inhibitory effects on the production of proin-flammatory cytokines (interleukin-1120573 (IL-1120573)) tumor necro-sis factor-120572 (TNF-120572) and monocyte chemoattractant pro-tein 1 (MCP-1) from lipopolysaccharide- (LPS-) stimulatedRAW2647 macrophages [98] Machado et al [99] showedthat Brazilian green propolis water extracts (PWE) modulatean anti-inflammatory cellular response in the model of LPS-induced pulmonary inflammation by decreasing the numberof macrophages and neutrophils Additionally it induced areduction in the secretion of IL-6 and TNF-120572 and an increasein TGF-120573 and IL-10 Another study showed that Brazilianred PEE promotes a significant decrease in renal macrophageinfiltration in rats with chronic kidney disease [100] Bufaloet al [101] demonstrated that Brazilian PEE and caffeicacid inhibited LPS-induced NO production by RAW2647macrophages acting at the transcriptional level and sug-gesting that their anti-inflammatory effects were mediatedby downregulating NF-120581B p38 MAP kinase and JNK12According to Naito et al [95] topical application of BrazilianPEE is effective in inhibiting carrageenan-induced rat hindpaw edemaThis sample appears to inhibit the chemotaxis ofhuman polymorphonuclear leukocytes (PMNs) which alsocontributes to its anti-inflammatory effects Another studyshowed the topical anti-inflammatory activity of propolisfrom Chile in mice ear with induced-edema In fact PEEfrom Buin Chile was the most active against the inflamma-tion induced by 12-O-tetradeca-noylphorbol-13-acetate andarachidonic acid and also inhibits significantly NO releaseby the macrophages [102] More recently Boudreau et al[103] indicated that CAPE is a potent leukotriene biosynthesisinhibitor in PMNs that blocks 5-lipoxygenase (5-LO) activityand arachidonic acid release A Croatian PEE may improvepsoriatic-like skin lesions whichwere induced in the study byirritant agents like n-hexyl salicylate or di-n-propyl disulfide

by reducing the lipid peroxidation in the skin and totalnumber of inflammatory cells in the skin and peritonealcavity more specially by suppressing functional activity ofmacrophages [104]

43 Immunomodulatory Activity Natural substances areconsidered alternative adjuvant therapies in the treatment ofdifferent diseases due to their immunomodulatory effectsInformation about this type of activity was scarce for propolisuntil the 1990s but published work in the last years has pro-vided information about the influence of different propolissamples on the immune system [65 105ndash112] (Table 4)

In a study using Brazilian green propolis it was seenthat the administration for 3 days of a PEE to male BALBcmice modulated the activation of the initial steps of theimmune response by upregulating toll-like receptor- (TLR-)2 and toll-like receptor-4 expression and proinflammatorycytokines (IL-1 and IL-6) production by macrophages andspleen cells [105] Another study demonstrated that BraziliangreenPEEupregulates TLR-4 andCD80 expression in humanmonocytes as well as TNF-120572 and IL-10 production [113] Itwas also shown that caffeic acid stimulates the activity ofmonocytes againstC albicans but it inhibits TLR-2 andHLA-DR expression as well as TNF-120572 and IL-10 production [114]

Additionally Missima et al [115] showed that Braziliangreen PEE administered to stressed mice reduces the proin-flammatory cytokines IL-1120573 and IL-6 When administered tomelanoma-bearing mice submitted or not to chronic stressit induces high levels of IL-1120573 and IL-6 and also stimu-lates Th1 cytokines production indicating the activation ofantitumour cell-mediated immunity Bachiega et al [116]investigated the immunomodulatory effect of propolis andcinnamic and coumaric acids on cytokines IL-1120573 IL-6 andIL-10 production Peritonealmacrophages fromBALBcmicewere incubated with different concentrations of propolis(5 50 and 100mgwell) and coumaric and cinnamic acid(50 and 100mgwell) Propolis and the acids stimulated IL-1120573 production and significantly inhibited IL-6 productionThen after LPS incubation the inhibitory concentrations ofcinnamic and coumaric acids prevented efficiently its effectson IL-6 production whereas propolis inhibited LPS effectsboth before and after its addition Additionally propolis andcoumaric and cinnamic acids inhibited IL-10 production Astudy which evaluated the effect of Brazilian green propolison macrophage activation by H

2O2and NO metabolite

determination [107] showed that propolis increased H2O2

generation and decreased NO generation which favoursthe microbicidal activity Recently the immunomodulatoryeffect of propolis collected in Brazil was evaluated in Leish-mania (Viannia) braziliensis experimental infection Datashows that macrophages incubated with propolis showed asignificant increase in interiorization and further killing ofparasites Also an increased TNF-120572 production was seen inpropolis-pretreated mice whereas IL-12 was downregulatedduring the infection [117]

The immunomodulatory action of propolis does notoccur only at the macrophage level In fact some studiesshow that this action has also an effect on lymphocyte pro-liferation [106 108] Sa-Nunes et al [108] showed inhibitory


Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik

ereceptor-2andreceptor-4

expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig

en-presentingcellsand

CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep

roliferationandreleaseo

fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep

roliferationandincrease

ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph

orylationandNF-120581Bactiv

ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]


effects of Brazilian green propolis on splenocyte proliferationeffect that was attributed to flavonoids and enhancementeffects on interferon- (IFN-) 120574 production by spleen cellsCAPE displays inhibitory effects on transcription factors NF-120581B and NFAT and as a consequence inhibits IL-2 genetranscription IL-2 receptor expression and proliferation ofhuman T cells [94] This provides new information into themolecular mechanisms involved in the anti-inflammatoryand immunomodulatory activities of propolis CAPE hasvarious biological activities but its effect on the immunomod-ulatory activity remains little studied According to Wanget al [112] CAPE can be useful in the treatment of asthmaand other allergic diseases because it can inhibit cytokinesand chemokines production by human monocyte-deriveddendritic cells (MoDCs) which might be related to theNF-120581B signalling pathway Another study demonstrated forthe first time that Brazilian propolis significantly inhibitedthe generation of Th1 cells Furthermore the effects ofpropolis were investigated on 246-trinitrobenzene sulfonicacid- (TNBS-) induced colitis in a mouse model Propolisreduced the frequency of IFN-120574-producing CD4 T cellsin a dose-dependent way under Th1-polarizing conditionsThe inhibitory effect of propolis on Th1 differentiation wasdemonstrated in vivo too and the severity of colitis inpropolis-fed mice was significantly lower than that of micefed with the control diet [118]

44 Antiviral Activity Propolis comprises a complexity ofcompounds which play a role in antiviral protection Despitethe few data available regarding this activity it was shown thatpropolis from different geographic regions has considerableantiviral activity by acting at different levels and interferingwith the replication of some viruses [12] like herpes simplextypes 1 and 2 adenovirus type 2 influenza virus or humanimmunodeficiency virus (HIV) among others [7 60 119ndash124] Table 5 summarizes the antiviral activity of propolis andits chemical constituents

Schnitzler et al [123] analysed the antiviral effect ofPWE and PEE from Czech Republic as well as that ofthe constituents caffeic acid p-coumaric acid benzoic acidgalangin pinocembrin and chrysin against herpes simplexvirus type 1 (HSV-1) in cell culture Both extracts exhibitedhigh anti-HSV-1 activity when cells were treated prior toviral infection galangin and chrysin being the main bioac-tive compounds Amoros et al [60] showed the antiviralactivity of the major flavonoids of propolis more specificallyflavonols and flavones the first being more active againstHSV-1 Additionally they analysed the effect of propolis onseveral DNA and RNA viruses (HSV-1 HSV-2 adenovirustype 2 vesicular stomatitis virus (VSV) and poliovirus type2) Propolis at a concentration of 30120583gmL reduced thetiter of herpes virus however vesicular stomatitis virusand adenovirus were less susceptible In addition propo-lis appears to exert a virucidal action on the envelopedviruses HSV and VSV [120] Recently it was shown thathydromethanolic extract of geopropolis from the stinglessbee Scaptotrigona postica (Brazil) inhibits theHSV replicationand also the entry of the virus into cells effect that wasattributed to the C-glycosyl flavones catechin-3-O-gallate

and 34-dicaffeoylquinic acid [125] According to Tait etal [126] natural and synthetic flavonoids might interferewith picornavirus replication preventing the decapsidationof viral particles and RNA release within cells or blockingviral RNA synthesis These authors also showed that differ-ent homoisoflavonoids have good antiviral activity againstthe coxsackie viruses B3 B4 and A9 and echovirus 30Shvarzbeyn and Huleihel [127] tried to determine whichstep of Tax oncoprotein-induced NF-120581B activation is blockedby propolis and CAPE and showed that both substantiallyinhibited the activation of NF-120581B-dependent promoter byTax Also they strongly prevented both Tax binding to I120581B120572and its induced degradation by Tax Ma et al [128] showedthat nanometer propolis flavones could significantly inhibitin vitro porcine parvovirus (PPV) infecting PK-15 cells andin vivo they restrain the PPV copy in lung gonad and blooddecrease the impact of PPV on weight of guinea pigs andincrease hemagglutination inhibition of PPV in serum as wellas improving the contents of IL-2 IL-6 and 120574-IFN

Over recent years therapeutic benefits of propolis andorits isolated compounds have been described in HIV treat-ment Ito et al [129] tested the anti-HIV activity in H9lymphocytes of triterpenoids melliferone moronic acidanwuweizonic acid and betulonic acid and four knownaromatic compounds isolated from Brazilian propolis andshowed that moronic acid had significant anti-HIV activityGekker et al [119] assessed the anti-HIV-1 activity of propolisin CD4+ lymphocytes and microglial cell cultures observ-ing the inhibition of viral expression in a concentration-dependent wayThe possible mechanism of propolis antiviralproperty was suggested to involve inhibition of viral entry

45 Antimicrobial Activity Antimicrobial activity one ofthe most studied propolis biological properties is very welldocumented This bioactivity has been largely investigatedin the last years due to the need of new treatments againstinfectious diseases especially with the increase of resistantpathogens to current antibiotics Tables 6 and 7 summarisethe antibacterial and antifungal activities found in propolisfrom different geographic origin andor its chemical con-stituents

451 Antibacterial Activity Propolis effect against severalbacterial strains has evaluated [7 56ndash59 130] and supportedthe fact that propolis is more active against Gram-positivebacteria than Gram-negative bacteria [12 59] Briefly datafrom different studies showed that propolis inhibits bac-terial motility and enzyme activity exhibits bacteriostaticactivity against different bacterial genera can be bactericidalin high concentrations and affects cytoplasmic membrane[130]

Mirzoeva et al [130] investigated the effect of PEEon the physiology of Bacillus subtilis Escherichia coli andRhodobacter sphaeroides proposing that propolis and someof its components like cinnamic acid and flavonoids affectthe ion permeability of the inner bacterial membrane causingthe dissipation of the membrane potential and inhibitingbacterial motility A recent study [131] provided valuableinformation for understanding the potential anti-H pylori


Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb

othextractswhencells

weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb

othextractswhenvirusesw

ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon

inflammatoryandoxidativep

rocessesreducingreactiv

especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str

ainH29Sacyclovirresistant

mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru

slesssusceptibleviru

cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV

replicationandentryinto

cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)

cellscoxsackieviruses

B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm

ice34-dicaffeoylquinica

cidwhich

increasesm

RNAlevelsof

tumor

necrosisfactor-related

apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis

34-dicaffeoylquinica

cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease

ofhemagglutinationinhibitio

nof

PPVin

serum

aswellasimprovingthe

contentsof

IL-2IL-6and120574-IFN

[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd

onorsmicroglialcellsiso

latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC

C27853andtwoclinicalisolates)and4clinicalisolates

ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm

onellaenteritidis(phage

type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six

methicillin-susceptib

leclinicalisolatesandsix

methicillin-resistant

clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive

bacteriaviabilityspecially

Saureus

andseveralofitsmethicillin-resistant

and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu

lacarbonariaCtorelliana

trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow

thofthetestedbacteria

[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains

(35Saureus63Sepidermidis

7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m

ethicillin-sensitive

andresistant

Saureus

Inhibitio

nof

Saureus

grow

thandbactericidalactiv

ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof

tuberculosisinfectionin

guinea-pigssince

itprom

otes

adecreaseinnecrosisform

ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial

microparticlesandsolubled

ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo

lisbasedgelspresentin

gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph

ogenetictypesseveralm

utants

ingenesinvolvedeither

inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop

olisbasedgelsandcream

which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth

ofthetestedbacteriain

different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw

ithclinicalfeatureso

fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]


mechanism of CAPE H pylori a major factor for gas-trointestinal illnesses contains the enzyme H pylori peptidedeformylase that catalyses the removal of formyl group fromthe N-terminus of nascent polypeptide chains Since theaction of this enzyme is essential for H pylori survival it isconsidered a promising therapeutic drug target Results fromabsorption spectra and crystal structural characterizationshowed that CAPE is a competitive inhibitor of peptidedeformylase blocking the substrate entrance and preventingsubstrate from approaching the active site [131]

It has been suggested that the combination of propoliswith other antibiotics would allow dose reduction of selectedantibiotics thus potentiating their effect The antibacterialactivity of Italian PEE in some clinically isolated Gram-positive strains as well as the synergetic effect with someantibiotics was assessed by Scazzocchio et al [56] Ital-ian PEE drastically increased the effect of ampicillin gen-tamycin and streptomycin and moderated the action ofchloramphenicol ceftriaxone and vancomycin No effectwas observed when used simultaneously with erythromycinWojtyczka et al [132] evaluated the in vitro antimicrobialactivity of a Polish PEE against methicillin-sensitive S aureus(MSSA) and methicillin-resistant S aureus (MRSA) clinicalisolates and also the combined effect of propolis with tenselected antistaphylococcal drugs PEE displayed varyingeffectiveness against twelve S aureus strains and potentiatedthe antimicrobial effect of eight antistaphylococcal againstall tested strains No synergism was observed in the caseof ciprofloxacin and chloramphenicol In another study theeffect of dichloromethane extract of French propolis againstdifferent human pathogenic bacterial strains was also testedAlthough Gram-negative bacteria were not susceptible tothe extract a significant antibacterial activity against bothmethicillin-resistant and methicillin-susceptible S aureusstrains was observed [133] The same was confirmed byVelikova et al [28] using different PEE from BulgariaGreece Turkey and Algeria All the samples showed agood antibacterial activity against S aureus but a week orlacking effect against E coli Australian PEE from stinglessbee Tetragonula carbonaria also inhibited the growth of Saureus Nevertheless it was less active against P aeruginosa[42] The same was observed by Papachroni et al [53]using PEE from Cameroon and CongoContrary to thesestudies Katircioglu and Mercan [134] showed that TurkishPEE was effective against Gram-negative bacteria like E coliOrsi et al [135] investigated the possible synergism betweenBrazilian and Bulgarian propolis and antibiotics acting onDNA (ciprofloxacin and norfloxacin) and on metabolism(cotrimoxazole) in Salmonella typhi Both samples hadantibacterial activity but no synergistic effect was detected

Recently the suitability of nanohydroxyapatite- (nano-HA-) based surfaces containing two Brazilian PEE (greenand red ones) to prevent S aureus bacterial growth andbiofilm was studied The nanoHA impregnated with thetwo highest concentrations (12 and 25120583gmL) of red PEEshowed a remarkable reduction of 99 in the number ofviable bacteria while nanoHA with green PEE at sameconcentrations showed a reduction of 45 and 61 Moreoverthe nanoHA impregnated with the highest concentration of

red PEE was able to inhibit 80 of the staphylococcal biofilmformation [136]

Diverse studies show that as the composition of propolisvaries from region to region the antibacterial activity alsodisplays some variations [59] Susceptibility of differentGram-positive bacteria to PEE varies with the place ofpropolis collection [137] The antibacterial effect was shownto be higher for samples from a wet-tropical rain forest-type climate Other studies revealed the influence of propolisgeographical origin on its antibacterial properties [57 58 138139] Propolis from the north and centre of Portugal has agreat activity against S aureus [58 140]

452 Antifungal Activity Antifungal activity is also influ-enced by the chemical variation of propolis [59] Severalstudies have shown the effect of propolis from differentgeographic origin against different fungi particularly ofclinical interest [141ndash145] Quiroga et al [146] demonstratedthe antifungal activity of propolis from the northwest ofArgentina focusing their study on the environment andthe development of agrochemicals with reduced economiccosts possibly containing propolis extracts and its isolatedcompounds such as pinocembrin and galangin as activeprinciples

Recently Falcao et al [140] screened the antifungalactivity of Portuguese propolis and its potential floral sourcesPopulus x Canadensis and Cistus ladanifer against Candidaalbicans Trichophyton rubrum and Aspergillus fumigatusPlant extracts did not exhibit relevant antifungal activity withexception of T rubrum but both propolis samples revealedsimilar antifungal activity the highest being obtained againstT rubrum and the lowest against A fumigatus A sample ofPEE from Poland showed a high fungicidal activity againstC albicans C glabrata and C krusei [147] Recently it wasshown that different organic extracts of French propolis (PEEPWEmethanolic extract and dichloromethane extract) wereeffective against C albicans and C glabrata but only have aweak activity towards A fumigates [133]

Brazilian PEE was proved to be active against severalCandida strains (C albicans C tropicalis C krusei andC guilliermondii) C albicans being the most sensitive andC guilliermondii the most resistant [141] Brazilian greenand red propolis display activity against different fungalspecies of Trichophyton which cause dermatophytosis redPEE being more efficient than the green one [143] Also itwas shown that n-hexane extract of Brazilian red propolisdid not induce resistance in Candida spp In fact it wasactive against Candida spp resistant to antifungal agentslike fluconazole [148] Dota et al [144] evaluated the in vitroantifungal activity of PEE and propolis microparticles (PMs)obtained from a sample from Argentina against clinical yeastisolates of importance in the vulvovaginal candidiasis Calbicans and non-C albicanswere inhibited by PEE and PMswith small variation Additionally it was shown that Braziliangreen PEE has the ability to inhibit growth and biofilmformation by C albicans from vulvovaginal candidiasis [149]Another study showed fungicide action of propolis (PEEPWE propolis matricial microparticles (PMM) and propolissoluble dry extract after 6ndash8-hour treatment against all three


C albicansmorphotypes (yeast pseudohyphae and hyphae)PEE being the most potent followed by PSDE PM andPWE [150] Brazilian propolis induces C albicans cell deathmediated via metacaspase since the metacaspase mutant inC albicans showed reduced sensitivity to propolis and bythe Ras pathway Using C albicans deletion libraries it waspossible to screen several mutants in genes involved eitherin the morphological transitions or in the maintenance of aspecific morphotype that are more sensitive to propolis Toconclude the study the authors also showed that propolisbased gels and cream were partially able to control vulvo-vaginal candidiasis in a mouse model [151] These studies[144] strongly indicate that propolis has a great potential tocontrol vulvovaginal candidiasis representing a promisingalternative therapeutic strategy

46 Antitumour Activity Recognition of the hallmarks ofcancer affects the search and development of new meth-ods and therapeutic agents with a sufficiently large thera-peutic window to kill tumour cells while sparing normalcells In the last years the natural product propolis hasattracted a growing interest by a large number of researcherssince it contains a variety of phytochemical compoundsthat may act through multiple pathways to reduce thedevelopment and other malignant characteristics of cancercells

Recently several in vitro studies have demonstrated acytotoxic action of propolis from different geographic originand of some of its isolated compounds on various tumourcells In vivo studies also show a potential in the developmentof new antitumor agents since propolis administration tomammals (eg rats) does not lead to detectable side effects[3] Briefly this natural product can block specific oncogenesignalling pathways which in turn lead to a decrease in cellproliferation and growth and can also act by decreasing thecancer stem cell population increasing apoptosis exertingantiangiogenic effects and modulating the tumour microen-vironment [66 152 153] Table 8 summarizes the antitumouractivity of propolis from different geographic origin and itschemical constituents

Some researchers showed the effect of different types ofpropolis and its constituents on cancer cell growth prolifera-tion and apoptosisThe hexane extract of propolis fromThai-land collected by the stingless bee Trigona laeviceps whichhas a different behavior in propolis collection compared tothe honey bees exerts antiproliferative activity against fivetested cancer cell lines (Chago KATO-III SW620 BT474and Hep-G2) but not against the normal cell lines tested(HS27 fibroblast and CH-liver) [5] A sample of PEE fromPoland inhibited human malignant melanoma (Me45) andcolorectal cancer (HCT 116) cells growth as well as reducedcell size [154]Other studies reported the antitumor activity ofBrazilianPEE [155ndash158]which regulate the protein expressionof cyclin D1 B1 and cyclin dependent kinase (CDK) as wellas p21 in human prostate cancer cells significantly affectingproliferation [158]

Although propolis containing CAPE is different fromthose with artepillin C it is possible to obtain a similarinhibitory effect from both types The effect of CAPE on

different cancer cell lines was analysed and many of itseffects have been shown to be mediated through inhibitionof NF-120581B [66 159] CAPE can inhibit the proliferation of thecolorectal cell line SW480 by decreasing the 120573-catenin c-myc and cyclin D1 protein expression [160] Chuu et al [161]observed that CAPE suppressed the proliferation of LNCaPDU-145 and PC-3 human prostate cancer cells in a dose-dependent manner and also inhibited the tumour growthof LNCaP xenografts in nude mice It was suggested that itacted through inhibition of p70S6K (an intermediary of thePI3KAKTpathway responsible for the protein synthesis) andsome Akt signalling networks Wu et al [162] demonstratedthat CAPE inhibits in vitro and in vivoMCF-7 andMDA-MB-231 tumour growthwithoutmuch effect on normalmammarycells by reducing the expression of growth and transcriptionfactors including NF-120581B Recently it was demonstrated thatCAPE effect on genes that are associated with tumour cellgrowth and survival is related in part to its role as a histonedeacetylase inhibitor [163]

As previously said propolis can also act by decreasingthe cancer stem cell population Using the putative CD44(+)CD24 (minuslow) breast cancer stem cells able to generatemammospheres from single cells Omene et al [164] showedthat CAPE caused a dose-dependent inhibition of cancerstem cells self-renewal progenitor formation and clonalgrowth

Concerning cell death some in vitro studies showeddifferent sensitivities of tumour cells to propolis extractsPWE from Iraq inhibits the proliferation of HL-60 cellsand leads to downregulation of Bcl-2 and activation of Bax[13] Alizadeh et al [165] investigated the protective effectsof Iranian PEE on N-methyl-N-nitro-N-nitrosoguanidine-(MNNG-) initiated gastric cancer in rats Results showedthat tumour incidence the number of lesions structuralabnormalities and beta-catenin of the animals group treatedwith PEE significantly declined compared with the controlPEE also induced the expression of proapoptotic Bax andreduced antiapoptotic Bcl-2 expression Propolis inhibitscolony formation potential and promotes necrotic changes inHCT-116 cells and decreases mitotic cells and increases p53and Ki-67 expression in HCT-116 tumor-bearing mice [13]Szliszkarsquos group have performed many studies to analyze theantitumour effect of different propolis and its constituentson prostate cancer cells (LNCaP and DU145) [166ndash168]Brazilian green PEE sensitized these cells to TRAIL-induceddeath enhanced the expression of TRAIL-R2 and decreasedthe activity of NF-120581B in LNCaP cells [167] Cotreatment ofTRAIL with artepillin C induced the significant activation ofcaspase-8 and caspase-3 as well as a significant disruption ofthe mitochondrial membrane potential [169] Many studieshave been conducted to understand the pathways involvedin the apoptotic effect of CAPE CAPE induces cell cyclearrest and apoptosis and reduces expression of NF-120581B inMDA-MB-231 and MCF-7 human breast cancer cells [162]In PC3 prostate cancer cells CAPE induced apoptosis in adose-dependent manner that was associated with the loss ofexpression of the inhibitors of apoptosis cIAP-1 cIAP-2 andXIAP [170] Cavaliere et al [171] showed that CAPE treatment


Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito

rsp21p27andp16decrease

intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-

dihydrocinnamoyloxy)

cinn

amicacid)a

ndartepillinC(isolated

from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man

prostatecancer-derived

cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin

N-butyl-(-4-hydroxybu

tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline

EAhy926renalcellcarcinom

acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572

proteinaccumulationwhich

attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and

NF2-deficientschwanno

ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC

sproliferationandinhibitio

nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof

TRAIL-R2anddecreasin

gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis

Biochemicals(SanDiego

CAU

SA)

Characteris

ticof

Brazilian

prop

olis

Quercetinkaempferoland

p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-

MB-231(ERminusPRminus

Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells

self-renewalprogenitorformation

andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof

MMP-2andmetalloproteinase-9

(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito

rmetalloproteinase-2

(TIM

P-2)

mRN

Alevels

downregulationof

MMP-2andMMP-9expressio

ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof

necroticchangesdecrease

ofmito

ticcells

andincrease

ofp53andKi-67expressio

nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero

flesionsstructuralabn

ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof

caspase-8andcaspase-3activ

ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia

l(Δ120595m)collapseindu

ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE

Fertilizedchickeneggs

Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum

ancolorectaladenocarcino

mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin

gcellviabilitypromotingcelldeathanddistu

rbingtumor

cellglycolyticmetabolism

[218]


of lymphoblastoid cell line PL104 induced apoptosis throughthe mitochondrial intrinsic pathway

It has been known that cancer microenvironment isvery important for carcinogenesis and it consists of stromalendothelial immune and cancer cells Natural productslike propolis and their constituents have been shown tointerfere with this symbiosis It was demonstrated by Lee et al[172] that CAPE could effectively suppress the adhesion andinvasion potential of human hepatocellular carcinoma cells(SK-Hep1) by inhibiting the expression ofMMP-2 andMMP-9 and NF-120581B

Angiogenesis has a crucial role in tumour growth dueto the requirement of oxygen and nutrients to sustain rapiduncontrolled proliferation and metastization Both tumourand stromal cells can secrete proangiogenic factors thatstimulate the formation andmaintenance of new vessels suchas vascular endothelial growth factor (VEGF) [173] BrazilianPEE could significantly reduce the number of newly formedvessels and suppress the proliferation of human umbilicalvein endothelial cells (HUVECs) [174] this antiangiogeniceffect being mainly mediated via inducing apoptosis in tube-forming endothelial cells through the inactivation of the sur-vival signal ERK12 [175] Yun et al [176] observed that CAPEinhibited angiogenesis using the in vivo assay chick embryochorioallantoic membrane (CAM) CAPE also suppressesVEGF formation by MDA-MB-231 cells and formation ofcapillary-like tubes by endothelial cells [162 177] Extractsof propolis containing artepillin C and CAPE significantlyreduced the newly formed vessels and expression of MMPsand VEGF production from various cells [178] and inaccordance with this study Izuta et al [179] described thatCAPE promotes inhibition of VEGF expression in HUVECcells

The first study on the antitumor activity of Portuguesepropolis was only performed in 2010 Using normal andcancerous renal cells derived from human renal cell carci-noma (RCC) patients in addition to A-498 cell line Valenteet al [64] showed that methanolic extract of Portuguesepropolis exhibited selective toxicity against malignant cellscompared to normal cells and in vitro RCC growth wasstrongly inhibited Recently our group demonstrated theantitumour and antiangiogenic activity of the ethanol extractof Pereiro propolis (P10EE) collected in the district ofGuarda Portugal P10EE affects cell viability of differenttumour cells MDA-MB-231 (breast) and DU145 (prostate)being two of the most sensitive ones but was less cytotoxicagainst nontumour cells and fibroblasts Also it signifi-cantly decreased MDA-MB-231 and DU145 cell prolifera-tion and migration along time with cell cycle changesand increased cell death The significant increase observedin glucose consumption and lactate production could beexplained in MDA-MB-231 by an increased expression ofhypoxia inducible factor-1120572 pyruvate dehydrogenase kinaseglucose transporter 1 lactate dehydrogenase and carbonicanhydrase Furthermore P10EE induced a decrease inHBMECs total biomass and proliferation and decreasedvessel sprouting in the chicken chorioallantoic membrane[23]

5 Conclusions

From ancient to modern times herbs and other plant prod-ucts have been widely used as medicinal agents first in folkmedicine and other activities in many parts of the world andlater developed and improved on a scientific basis into drugsthat are used in the health system Propolis is one of thefew natural products that has maintained its popularity overa long period of time As reviewed here propolis containsa broad spectrum of compounds that may be useful in thetreatment of different pathological conditions In fact there ismuch literature that deals with the in vitro and in vivo biologi-cal properties of propolisThis wide range of bioactivities thecontinuous discovery of new compounds the long history ofpropolis use and its safety profile make propolis a potentialcandidate for drug discovery that may be useful in severalclinical scenarios Nevertheless it is necessary to make aneffort to standardize propolis composition since it seems thatpropolis biological properties and chemical composition notonly are variable but also are strictly linked In our opinionpropolis extracts may be important economically and wouldallow a relatively inexpensive treatment in different diseaseshowever to promote its use in modern medicine it will benecessary to identify and isolate the bioactive compoundsto be tested separately or in combination with other drugsalready available

Drug discovery does not consist only of the isolationof bioactive lead compounds from the natural sources Infact this process continues outside the academic laboratoriesthrough preclinical studies followed by clinical trials Thusdespite the in vitro and in vivo assays which provide newvaluable information on propolis biological properties andmechanisms of action it will be necessary to analyse theeffectiveness of propolis clinically to complement the basicresearch available and to evaluate the potential of propolis inhuman health promotion

Abbreviations

CAPE Caffeic acid phenethyl esterPEE Propolis ethanol extractPWE Propolis water extractRNS Reactive nitrogen speciesROS Reactive oxygen speciesVEGF Vascular endothelial growth factor

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

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[2] D J Newman and G M Cragg ldquoNatural products as sources ofnew drugs over the last 25 yearsrdquo Journal of Natural Productsvol 70 no 3 pp 461ndash477 2007


[3] M A E Watanabe M K Amarante B J Conti and J MSforcin ldquoCytotoxic constituents of propolis inducing anticancereffects a reviewrdquo Journal of Pharmacy and Pharmacology vol63 no 11 pp 1378ndash1386 2011

[4] K-H Lee ldquoCurrent developments in the discovery and designof new drug candidates from plant natural product leadsrdquoJournal of Natural Products vol 67 no 2 pp 273ndash283 2004

[5] S Umthong P Phuwapraisirisan S Puthong andC ChanchaoldquoIn vitro antiproliferative activity of partially purified Trigonalaeviceps propolis from Thailand on human cancer cell linesrdquoBMC Complementary and Alternative Medicine vol 11 article37 2011

[6] J M Sforcin and V Bankova ldquoPropolis is there a potential forthe development of new drugsrdquo Journal of Ethnopharmacologyvol 133 no 2 pp 253ndash260 2011

[7] MMarcucci ldquoPropolis chemical composition biological prop-erties and therapeutic activityrdquoApidologie vol 26 no 2 pp 83ndash99 1995

[8] Y Barlak O Deger M Colak S C Karatayli A M Bozdayiand F Yucesan ldquoEffect of Turkish propolis extracts on proteomeof prostate cancer cell linerdquo Proteome Science vol 9 article 742011

[9] V Bankova ldquoChemical diversity of propolis and the problem ofstandardizationrdquo Journal of Ethnopharmacology vol 100 no 1-2 pp 114ndash117 2005

[10] V S Bankova S L de Castro and M C Marcucci ldquoPropolisrecent advances in chemistry and plant originrdquo Apidologie vol31 no 1 pp 3ndash15 2000

[11] S M Cardoso M Ribeiro I L Ferreira and A Cristina RegoldquoNortheast Portuguese propolis protects against staurosporineand hydrogen peroxide-induced neurotoxicity in primary cor-tical neuronsrdquo Food and Chemical Toxicology vol 49 no 11 pp2862ndash2868 2011

[12] H Fokt A Pereira A M Ferreira A Cunha and C AguiarldquoHow do bees prevent hive infections The antimicrobial prop-erties of propolisrdquo in Current Research Technology and Educa-tion Topics in AppliedMicrobiology andMicrobial BiotechnologyA Mendez-Vilas Ed vol 1 of Microbiology Book SeriesmdashNumber 2 pp 481ndash493 2010

[13] G M Sulaiman A H Adrsquohiah K W Al-Sammarrae et alldquoAssessing the anti-tumour properties of Iraqi propolis in vitroand in vivordquo Food and Chemical Toxicology vol 50 no 5 pp1632ndash1641 2012

[14] N Orsolic S Terzic Z Mihaljevic L Sver and I BasicldquoEffects of local administration of propolis and its polyphenoliccompounds on tumor formation and growthrdquo Biological andPharmaceutical Bulletin vol 28 no 10 pp 1928ndash1933 2005

[15] S Castaldo and F Capasso ldquoPropolis an old remedy used inmodern medicinerdquo Fitoterapia vol 73 supplement 1 pp S1ndashS62002

[16] G A Burdock ldquoReview of the biological properties and toxicityof bee propolis (propolis)rdquo Food and Chemical Toxicology vol36 no 4 pp 347ndash363 1998

[17] M L Khalil ldquoBiological activity of bee propolis in health anddiseaserdquo Asian Pacific Journal of Cancer Prevention vol 7 no 1pp 22ndash31 2006

[18] J B Daleprane V da Silva Freitas A Pacheco et al ldquoAnti-atherogenic and anti-angiogenic activities of polyphenols frompropolisrdquo Journal of Nutritional Biochemistry vol 23 no 6 pp557ndash566 2012

[19] A H Banskota Y Tezuka and S Kadota ldquoRecent progress inpharmacological research of propolisrdquo Phytotherapy Researchvol 15 no 7 pp 561ndash571 2001

[20] S I Falcao M Vilas-Boas L M Estevinho C Barros M R MDomingues and S M Cardoso ldquoPhenolic characterization ofNortheast Portuguese propolis usual and unusual compoundsrdquoAnalytical and Bioanalytical Chemistry vol 396 no 2 pp 887ndash897 2010

[21] S I Falcao N Vale P Gomes et al ldquoPhenolic profilingof Portuguese propolis by LC-MS spectrometry uncommonpropolis rich in flavonoid glycosidesrdquo Phytochemical Analysisvol 24 no 4 pp 309ndash318 2013

[22] L-P Sun A-L Chen H-C Hung et al ldquoChrysin a histonedeacetylase 8 inhibitor with anticancer activity and a suitablecandidate for the standardization of Chinese propolisrdquo Journalof Agricultural and Food Chemistry vol 60 no 47 pp 11748ndash11758 2012

[23] R Silva-Carvalho V Miranda-Goncalves A M Ferreira etal ldquoAntitumoural and antiangiogenic activity of Portuguesepropolis in in vitro and in vivo modelsrdquo Journal of FunctionalFoods vol 11 pp 160ndash171 2014

[24] M P Popova K Graikou I Chinou and V S Bankova ldquoGC-MS profiling of diterpene compounds in mediterranean propo-lis fromGreecerdquo Journal of Agricultural andFoodChemistry vol58 no 5 pp 3167ndash3176 2010

[25] O G Celemli F Hatjina L Charistos A Schiesser and AOzkirim ldquoMore insight into the chemical composition of Greekpropolis differences and similarities with Turkish propolisrdquoZeitschrift fur Naturforschung C vol 68 no 11-12 pp 429ndash4382013

[26] V Bankova M Popova S Bogdanov and A-G SabatinildquoChemical composition of European propolis expected andunexpected resultsrdquo Zeitschrift fur Naturforschung Section Cvol 57 no 5-6 pp 530ndash533 2002

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[28] M Velikova V Bankova K Sorkun S Houcine I Tsvetkovaand A Kujumgiev ldquoPropolis from the Mediterranean regionchemical composition and antimicrobial activityrdquoZeitschrift furNaturforschung C vol 55 no 9-10 pp 790ndash793 2000

[29] S Silici M Unlu and G Vardar-Unlu ldquoAntibacterial activityand phytochemical evidence for the plant origin of Turkishpropolis from different regionsrdquoWorld Journal of Microbiologyand Biotechnology vol 23 no 12 pp 1797ndash1803 2007

[30] N Duran M Muz G Culha G Duran and B Ozer ldquoGC-MSanalysis and antileishmanial activities of two Turkish propolistypesrdquo Parasitology Research vol 108 no 1 pp 95ndash105 2011

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Evidence-Based Complementary and Alternative Medicine vol5 no 4 pp 435ndash441 2008

[35] B B Silva P L Rosalen J A Cury et al ldquoChemical compositionand botanical origin of red propolis a new type of Brazil-ian propolisrdquo Evidence-Based Complementary and AlternativeMedicine vol 5 no 3 pp 313ndash316 2008

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[37] B Trusheva M Popova H Naydenski I Tsvetkova J GRodriguez andV Bankova ldquoNew polyisoprenylated benzophe-nones from Venezuelan propolisrdquo Fitoterapia vol 75 no 7-8pp 683ndash689 2004

[38] F A Tomas-Barberan C Garcıa-Viguera P Vit-Olivier FFerreres and F Tomas-Lorente ldquoPhytochemical evidence forthe botanical origin of tropical propolis from VenezuelardquoPhytochemistry vol 34 no 1 pp 191ndash196 1993

[39] A Abu-Mellal N Koolaji R K Duke V H Tran and CC Duke ldquoPrenylated cinnamate and stilbenes from KangarooIsland propolis and their antioxidant activityrdquo Phytochemistryvol 77 pp 251ndash259 2012

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Clinical Reviews in Allergy and Immunology vol 44 no 3 pp262ndash273 2013

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[73] R Schnabel and S Blankenberg ldquoOxidative stress in cardiovas-cular disease successful translation from bench to bedsiderdquoCirculation vol 116 no 12 pp 1338ndash1340 2007

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[75] M A Nader D S El-Agamy and G M Suddek ldquoProtectiveeffects of propolis and thymoquinone on development ofatherosclerosis in cholesterol-fed rabbitsrdquo Archives of Pharma-cal Research vol 33 no 4 pp 637ndash643 2010

[76] A Scalbert I T Johnson and M Saltmarsh ldquoPolyphenolsantioxidants and beyondrdquo The American Journal of ClinicalNutrition vol 81 no 1 supplement pp 215Sndash217S 2005

[77] N Almaraz-Abarca M da Graca Campos J A Avila-Reyes NNaranjo-Jimenez J Herrera Corral and L S Gonzalez-ValdezldquoAntioxidant activity of polyphenolic extract of monofloralhoneybee-collected pollen from mesquite (Prosopis julifloraLeguminosae)rdquo Journal of Food Composition and Analysis vol20 no 2 pp 119ndash124 2007

[78] S Fabris M Bertelle O Astafyeva et al ldquoAntioxidant proper-ties and chemical composition relationship of europeans andBrazilians propolisrdquo Pharmacology amp Pharmacy vol 4 no 1pp 46ndash51 2013

[79] C M Mihai L A Marghitas D S Daniel S Dezmireanand L Barnutiu ldquoCorrelation between polyphenolic profileand antioxidant activity of propolis from Transylvaniardquo AnimalScience and Biotechnologies vol 44 no 2 pp 100ndash103 2011

[80] G G Duthie P T Gardner and J A M Kyle ldquoPlant polyphe-nols are they the newmagic bulletrdquoProceedings of theNutritionSociety vol 62 no 3 pp 599ndash603 2003

[81] H Yang Y Dong H Du H Shi Y Peng and X Li ldquoAntiox-idant compounds from propolis collected in Anhui ChinardquoMolecules vol 16 no 4 pp 3444ndash3455 2011

[82] V Silva G Genta M N Moller et al ldquoAntioxidant activityof Uruguayan propolis In vitro and cellular assaysrdquo Journal ofAgricultural and Food Chemistry vol 59 no 12 pp 6430ndash64372011

[83] P Bolfa R Vidrighinescu A Petruta et al ldquoPhotoprotectiveeffects of Romanian propolis on skin of mice exposed to UVBirradiationrdquo Food andChemical Toxicology vol 62 pp 329ndash3422013

[84] Z Talas I Ozdemir O Ciftci M Gulhan and A SavcildquoAntioxidant effect of ethanolic extract of propolis in liver ofL-name treated ratsrdquo Advances in Clinical and ExperimentalMedicine vol 24 no 2 pp 227ndash232 2015

[85] A Russo R Longo and A Vanella ldquoAntioxidant activity ofpropolis role of caffeic acid phenethyl ester and galanginrdquoFitoterapia vol 73 supplement 1 pp S21ndashS29 2002

[86] M Hosnuter A Gurel O Babuccu F Armutcu E Kargi andA Isikdemir ldquoThe effect of CAPE on lipid peroxidation andnitric oxide levels in the plasmaof rats following thermal injuryrdquoBurns vol 30 no 2 pp 121ndash125 2004

[87] Y-J Chen A-C Huang H-H Chang et al ldquoCaffeic acidphenethyl ester an antioxidant from propolis protects periph-eral blood mononuclear cells of competitive cyclists againsthyperthermal stressrdquo Journal of Food Science vol 74 no 6 ppH162ndashH167 2009

[88] S Reuter S C Gupta M M Chaturvedi and B B AggarwalldquoOxidative stress inflammation and cancer how are theylinkedrdquo Free Radical Biology and Medicine vol 49 no 11 pp1603ndash1616 2010

[89] G Costa V Francisco M C Lopes M T Cruz and MT Batista ldquoIntracellular signaling pathways modulated byphenolic compounds application for new anti-inflammatorydrugs discoveryrdquo Current Medicinal Chemistry vol 19 no 18pp 2876ndash2900 2012

[90] O K Mirzoeva and P C Calder ldquoThe effect of propolis and itscomponents on eicosanoid production during the inflamma-tory responserdquo Prostaglandins Leukotrienes and Essential FattyAcids vol 55 no 6 pp 441ndash449 1996

[91] A Rossi A Ligresti R Longo A Russo F Borrelli andL Sautebin ldquoThe inhibitory effect of propolis and caf-feic acid phenethyl ester on cyclooxygenase activity in J774macrophagesrdquo Phytomedicine vol 9 no 6 pp 530ndash535 2002

[92] S Chirumbolo ldquoThe role of quercetin flavonols and flavonesin modulating inflammatory cell functionrdquo Inflammation andAllergymdashDrug Targets vol 9 no 4 pp 263ndash285 2010

[93] E-H Park and J-H Kahng ldquoSuppressive effects of propolis inrat adjuvant arthritisrdquo Archives of Pharmacal Research vol 22no 6 pp 554ndash558 1999

[94] N Marquez R Sancho A Macho M A Calzado B L Fiebichand E Munoz ldquoCaffeic acid phenethyl ester inhibits T-cellactivation by targeting both nuclear factor of activated T-cellsand NF-120581B transcription factorsrdquo Journal of Pharmacology andExperimental Therapeutics vol 308 no 3 pp 993ndash1001 2004

[95] Y Naito M Yasumuro K Kondou and N Ohara ldquoAnti-inflammatory effect of topically applied propolis extractin carrageenan-induced rat hind paw edemardquo PhytotherapyResearch vol 21 no 5 pp 452ndash456 2007

[96] M Funakoshi-Tago K Okamoto R Izumi et al ldquoAnti-inflammatory activity of flavonoids in Nepalese propolis isattributed to inhibition of the IL-33 signaling pathwayrdquo Inter-national Immunopharmacology vol 25 no 1 pp 189ndash198 2015

[97] R M N Bezerra L F Veiga A C Caetano et al ldquoCaffeicacid phenethyl ester reduces the activation of the nuclear factorkappab pathway by high-fat diet-induced obesity in micerdquoMetabolism Clinical and Experimental vol 61 no 11 pp 1606ndash1614 2012


[98] S Juman N Yasui K Ikeda et al ldquoCaffeic acid phenethylester suppresses the production of pro-inflammatory cytokinesin hypertrophic adipocytes through lipopolysaccharide-stimulated macrophagesrdquo Biological and PharmaceuticalBulletin vol 35 no 11 pp 1941ndash1946 2012

[99] J L Machado A K Assuncao M C da Silva et alldquoBrazilian green propolis anti-inflammatory property by animmunomodulatory activityrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 157652 10 pages2012

[100] F Teles T M da Silva F P da Cruz Junior et al ldquoBrazilian redpropolis attenuates hypertension and renal damage in 56 renalablation modelrdquo PLoS ONE vol 10 no 1 Article ID e01165352015

[101] M C Bufalo I Ferreira G Costa et al ldquoPropolis andits constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-120581B and MAPK activa-tion in macrophagesrdquo Journal of Ethnopharmacology vol 149no 1 pp 84ndash92 2013

[102] G Valenzuela-Barra C Castro C Figueroa et al ldquoAnti-inflammatory activity and phenolic profile of propolis from twolocations in Region Metropolitana de Santiago Chilerdquo Journalof Ethnopharmacology vol 168 pp 37ndash44 2015

[103] L H Boudreau J Maillet L M LeBlanc et al ldquoCaffeic acidphenethyl ester and its amide analogue are potent inhibitors ofleukotriene biosynthesis in human polymorphonuclear leuko-cytesrdquo PLoS ONE vol 7 no 2 Article ID e31833 2012

[104] N Orsolic J Skuric D Crossed D Signikic and G StanicldquoInhibitory effect of a propolis on Di-n-Propyl Disulfide orn-Hexyl salycilate-induced skin irritation oxidative stress andinflammatory responses in micerdquo Fitoterapia vol 93 pp 18ndash302014

[105] C L Orsatti F Missima A C Pagliarone et al ldquoPropolisimmunomodulatory action in vivo on toll-like receptors 2 and4 expression and on pro-inflammatory cytokines production inmicerdquo Phytotherapy Research vol 24 no 8 pp 1141ndash1146 2010

[106] N Ivanovska H Neychev Z Stefanova V Bankova andS Popov ldquoInfluence of cinnamic acid on lymphocyte pro-liferation cytokine release and Klebsiella infection in micerdquoApidologie vol 26 no 2 pp 73ndash81 1995

[107] R O Orsi S R Funari A M V C Soares and et alldquoImmunomodulatory action of propolis onmacrophage activa-tionrdquo Journal of Venomous Animals and Toxins vol 6 no 2 pp205ndash219 2000

[108] A Sa-Nunes L H Faccioli and J M Sforcin ldquoPropolisLymphocyte proliferation and IFN-120574 productionrdquo Journal ofEthnopharmacology vol 87 no 1 pp 93ndash97 2003

[109] F Missima and J M Sforcin ldquoGreen Brazilian propolisaction on macrophages and lymphoid organs of chronicallystressed micerdquo Evidence-Based Complementary and AlternativeMedicine vol 5 no 1 pp 71ndash75 2008

[110] Syamsudin R M Dewi and Kusmardi ldquoImmunomodulatoryand in vivo antiplasmodial activities of propolis extractsrdquoAmerican Journal of Pharmacology and Toxicology vol 4 no3 pp 75ndash79 2009

[111] C L Orsatti and J M Sforcin ldquoPropolis immunomodulatoryactivity on TLR-2 and TLR-4 expression by chronically stressedmicerdquo Natural Product Research vol 26 no 5 pp 446ndash4532012

[112] L-C Wang Y-L Lin Y-C Liang et al ldquoThe effect of caffeicacid phenethyl ester on the functions of human monocyte-derived dendritic cellsrdquo BMC Immunology vol 10 article 392009

[113] M C Bufalo A P Bordon-Graciani B J Conti M de AssisGolim and J M Sforcin ldquoThe immunomodulatory effect ofpropolis on receptors expression cytokine production andfungicidal activity of human monocytesrdquo Journal of Pharmacyand Pharmacology vol 66 no 10 pp 1497ndash1504 2014

[114] MC Bufalo and JM Sforcin ldquoThemodulatory effects of caffeicacid on human monocytes and its involvement in propolisactionrdquo Journal of Pharmacy and Pharmacology vol 67 no 5pp 740ndash745 2015

[115] F Missima A C Pagliarone C L Orsatti and J M SforcinldquoThe effect of propolis on pro-inflammatory cytokines pro-duced by melanoma-bearing mice submitted to chronic stressrdquoJournal of ApiProduct amp ApiMedical Science vol 1 no 1 pp 11ndash15 2009

[116] T F Bachiega C L Orsatti A C Pagliarone and J M SforcinldquoThe effects of propolis and its isolated compounds on cytokineproduction by murine macrophagesrdquo Phytotherapy Researchvol 26 no 9 pp 1308ndash1313 2012

[117] S S da Silva S Thome Gda A H Cataneo et al ldquoBrazil-ian propolis antileishmanial and immunomodulatory effectsrdquoEvidence-Based Complementary and Alternative Medicine vol2013 Article ID 673058 7 pages 2013

[118] Y Okamoto T Hara T Ebato T Fukui and T MasuzawaldquoBrazilian propolis ameliorates trinitrobenzene sulfonic acid-induced colitis in mice by inhibiting Th1 differentiationrdquo Inter-national Immunopharmacology vol 16 no 2 pp 178ndash183 2013

[119] G Gekker S Hu M Spivak J R Lokensgard and P KPeterson ldquoAnti-HIV-1 activity of propolis in CD4+ lymphocyteandmicroglial cell culturesrdquo Journal of Ethnopharmacology vol102 no 2 pp 158ndash163 2005

[120] M Amoros F Sauvager L Girre and M Cormier ldquoIn vitroantiviral activity of propolisrdquo Apidologie vol 23 no 3 pp 231ndash240 1992

[121] J Serkedjieva N Manolova and V Bankova ldquoAnti-influenzavirus effect of some propolis constituents and their analogues(esters of substituted cinnamic acids)rdquo Journal of NaturalProducts vol 55 no 3 pp 294ndash297 1992

[122] T Shimizu A Hino A Tsutsumi Y K Park WWatanabe andM Kurokawa ldquoAnti-influenza virus activity of propolis in vitroand its efficacy against influenza infection in micerdquo AntiviralChemistry and Chemotherapy vol 19 no 1 pp 7ndash13 2008

[123] P Schnitzler A Neuner S Nolkemper et al ldquoAntiviral activityand mode of action of propolis extracts and selected com-poundsrdquo Phytotherapy Research vol 24 supplement 1 pp S20ndashS28 2010

[124] G Sartori A P Pesarico S Pinton et al ldquoProtective effect ofbrown Brazilian propolis against acute vaginal lesions caused byherpes simplex virus type 2 in mice involvement of antioxidantand anti-inflammatory mechanismsrdquo Cell Biochemistry andFunction vol 30 no 1 pp 1ndash10 2012

[125] G R Coelho R ZMendonca KDVilar et al ldquoAntiviral actionof hydromethanolic extract of geopropolis from Scaptotrigonapostica against antiherpes simplex virus (HSV-1)rdquo Evidence-Based Complementary and Alternative Medicine vol 2015Article ID 296086 10 pages 2015

[126] S Tait A L Salvati N Desideri and L Fiore ldquoAntiviral activityof substituted homoisoflavonoids on enterovirusesrdquo AntiviralResearch vol 72 no 3 pp 252ndash255 2006


[127] J Shvarzbeyn and M Huleihel ldquoEffect of propolis and caffeicacid phenethyl ester (CAPE) on NF120581B activation by HTLV-1Taxrdquo Antiviral Research vol 90 no 3 pp 108ndash115 2011

[128] X Ma Z Guo Z Shen Y Liu J Wang and Y Fan ldquoTheanti-porcine parvovirus activity of nanometer propolis flavoneand propolis flavone in vitro and in vivordquo Evidence-BasedComplementary and Alternative Medicine vol 2015 Article ID472876 10 pages 2015

[129] J Ito F-R Chang H-K Wang et al ldquoAnti-AIDS agents48 Anti-HIV activity of moronic acid derivatives and thenew melliferone-related triterpenoid isolated from Brazilianpropolisrdquo Journal of Natural Products vol 64 no 10 pp 1278ndash1281 2001

[130] O K Mirzoeva R N Grishanin and P C Calder ldquoAntimi-crobial action of propolis and some of its components theeffects on growthmembrane potential andmotility of bacteriardquoMicrobiological Research vol 152 no 3 pp 239ndash246 1997

[131] K Cui W Lu L Zhu X Shen and J Huang ldquoCaffeic acidphenethyl ester (CAPE) an active component of propolisinhibits Helicobacter pylori peptide deformylase activityrdquo Bio-chemical and Biophysical Research Communications vol 435no 2 pp 289ndash294 2013

[132] R D Wojtyczka A Dziedzic D Idzik et al ldquoSusceptibility ofStaphylococcus aureus clinical isolates to propolis extract aloneor in combination with antimicrobial drugsrdquoMolecules vol 18no 8 pp 9623ndash9640 2013

[133] S Boisard A Le Ray A Landreau et al ldquoAntifungal andantibacterial metabolites from a French poplar type propolisrdquoEvidence-Based Complementary and Alternative Medicine vol2015 Article ID 319240 10 pages 2015

[134] H Katircioglu and N Mercan ldquoAntimicrobial activity andchemical compositions of Turkish propolis from differentregionsrdquoAfrican Journal of Biotechnology vol 5 no 11 pp 1151ndash1153 2006

[135] R O Orsi A Fernandes Jr V Bankova and J M SforcinldquoAntibacterial effects of Brazilian and Bulgarian propolis andsynergistic effects with antibiotics acting on the bacterial DNAand folic acidrdquoNatural Product Research vol 26 no 4 pp 344ndash349 2012

[136] L Grenho J Barros C Ferreira et al ldquoIn vitro antimicrobialactivity and biocompatibility of propolis containing nanohy-droxyapatiterdquo Biomedical Materials vol 10 no 2 Article ID025004 2015

[137] V Seidel E Peyfoon D G Watson and J Fearnley ldquoCompara-tive study of the antibacterial activity of propolis from differentgeographical and climatic zonesrdquo Phytotherapy Research vol22 no 9 pp 1256ndash1263 2008

[138] L Monzote O Cuesta-Rubio M C Fernandez et al ldquoIn vitroantimicrobial assessment ofCubanpropolis extractsrdquoMemoriasdo Instituto Oswaldo Cruz vol 107 no 8 pp 978ndash984 2012

[139] L G Dias A P Pereira and L M Estevinho ldquoComparativestudy of different Portuguese samples of propolis pollinicsensorial physicochemical microbiological characterizationand antibacterial activityrdquo Food and Chemical Toxicology vol50 no 12 pp 4246ndash4253 2012

[140] S I Falcao N Vale P Cos et al ldquoIn vitro evaluationof portuguese propolis and floral sources for antiprotozoalantibacterial and antifungal activityrdquo Phytotherapy Researchvol 28 no 3 pp 437ndash443 2014

[141] C Ota C Unterkircher V Fantinato and M T ShimizuldquoAntifungal activity of propolis on different species of CandidardquoMycoses vol 44 no 9-10 pp 375ndash378 2001

[142] J M Murad S A Calvi A M V C Soares V Bankova andJ M Sforcin ldquoEffects of propolis from Brazil and Bulgariaon fungicidal activity of macrophages against Paracoccidioidesbrasiliensisrdquo Journal of Ethnopharmacology vol 79 no 3 pp331ndash334 2002

[143] A B S Siqueira B S Gomes I Cambuim et al ldquoTrichophytonspecies susceptibility to green and red propolis from BrazilrdquoLetters in Applied Microbiology vol 48 no 1 pp 90ndash96 2009

[144] K F D Dota M E L Consolaro T I E Svidzinski and ML Bruschi ldquoAntifungal activity of brazilian propolis micropar-ticles against yeasts isolated from vulvovaginal candidiasisrdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 201953 8 pages 2011

[145] J S Bonvehı and A L Gutierrez ldquoThe antimicrobial effects ofpropolis collected in different regions in the Basque Country(Northern Spain)rdquo World Journal of Microbiology and Biotech-nology vol 28 no 4 pp 1351ndash1358 2012

[146] E N Quiroga D A Sampietro J R Soberon M A SgarigliaandM A Vattuone ldquoPropolis from the northwest of Argentinaas a source of antifungal principlesrdquo Journal of Applied Microbi-ology vol 101 no 1 pp 103ndash110 2006

[147] P Szweda K Gucwa E Kurzyk et al ldquoEssential oils silvernanoparticles and propolis as alternative agents against flucona-zole resistant Candida albicans Candida glabrata and Candidakrusei clinical isolatesrdquo Indian Journal of Microbiology vol 55no 2 pp 175ndash183 2015

[148] B Pippi A Lana R Moraes et al ldquoIn vitro evaluation of theacquisition of resistance antifungal activity and synergism ofBrazilian red propolis with antifungal drugs on Candida spprdquoJournal of Applied Microbiology vol 118 no 4 pp 839ndash8502015

[149] I R G Capoci P de Souza Bonfim-Mendonca G S Arita etal ldquoPropolis is an efficient fungicide and inhibitor of biofilmproduction by vaginal Candida albicansrdquo Evidence-Based Com-plementary and Alternative Medicine vol 2015 Article ID287693 9 pages 2015

[150] A A Berretta P A de Castro A H Cavalheiro et alldquoEvaluation of mucoadhesive gels with propolis (EPP-AF) inpreclinical treatment of candidiasis vulvovaginal infectionrdquoEvidence-Based Complementary and Alternative Medicine vol2013 Article ID 641480 18 pages 2013

[151] P A De Castro V L P Bom N A Brown et al ldquoIdentificationof the cell targets important for propolis-induced cell death inCandida albicansrdquo Fungal Genetics and Biology vol 60 pp 74ndash86 2013

[152] D Sawicka H Car M H Borawska and J Niklinski ldquoThe anti-cancer activity of propolisrdquo Folia Histochemica et Cytobiologicavol 50 no 1 pp 25ndash37 2012

[153] J R Araujo P Goncalves and F Martel ldquoChemopreventiveeffect of dietary polyphenols in colorectal cancer cell linesrdquoNutrition Research vol 31 no 2 pp 77ndash87 2011

[154] R Kubina A Kabała-Dzik A Dziedzic et al ldquoThe ethanolextract of polish propolis exhibits anti-proliferative andor pro-apoptotic effect on HCT 116 colon cancer and me45 malignantmelanoma cells in vitro conditionsrdquo Advances in Clinical andExperimental Medicine vol 24 no 2 pp 203ndash212 2015

[155] M Ishihara KNaoiMHashita Y Itoh andM Suzui ldquoGrowthinhibitory activity of ethanol extracts of Chinese and Brazilianpropolis in four human colon carcinoma cell linesrdquo OncologyReports vol 22 no 2 pp 349ndash354 2009

[156] S M Messerli M-R Ahn K Kunimasa et al ldquoArtepillin C(ARC) in Brazilian green propolis selectively blocks oncogenic


PAK1 signaling and suppresses the growth of NF tumors inmicerdquo Phytotherapy Research vol 23 no 3 pp 423ndash427 2009

[157] S Awale F Li H Onozuka H Esumi Y Tezuka and S KadotaldquoConstituents of Brazilian red propolis and their preferentialcytotoxic activity against human pancreatic PANC-1 cancer cellline in nutrient-deprived conditionrdquo Bioorganic amp MedicinalChemistry vol 16 no 1 pp 181ndash189 2008

[158] H Li A Kapur J X Yang et al ldquoAntiproliferation of humanprostate cancer cells by ethanolic extracts of Brazilian propolisand its botanical originrdquo International Journal of Oncology vol31 no 3 pp 601ndash606 2007

[159] G Ozturk Z Ginis S Akyol G Erden A Gurel and OAkyol ldquoThe anticancer mechanism of caffeic acid phenethylester (CAPE) review of melanomas lung and prostate cancersrdquoEuropean Review for Medical and Pharmacological Sciences vol16 no 15 pp 2064ndash2068 2012

[160] Y-J He B-H Liu D-B Xiang Z-Y Qiao T Fu and Y-HHe ldquoInhibitory effect of caffeic acid phenethyl ester on thegrowth of SW480 colorectal tumor cells involves 120573-cateninassociated signaling pathway down-regulationrdquo World Journalof Gastroenterology vol 12 no 31 pp 4981ndash4985 2006

[161] C-P Chuu H-P Lin M F Ciaccio et al ldquoCaffeic acidphenethyl ester suppresses the proliferation of human prostatecancer cells through inhibition of p70S6K and Akt signalingnetworksrdquo Cancer Prevention Research vol 5 no 5 pp 788ndash797 2012

[162] J Wu C Omene J Karkoszka et al ldquoCaffeic acid phenethylester (CAPE) derived from a honeybee product propolisexhibits a diversity of anti-tumor effects in pre-clinical modelsof human breast cancerrdquo Cancer Letters vol 308 no 1 pp 43ndash53 2011

[163] C Omene M Kalac J Wu E Marchi K Frenkel and OA OrsquoConnor ldquoPropolis and its active component caffeic acidphenethyl ester (CAPE) modulate breast cancer therapeutictargets via an epigenetically mediated mechanism of actionrdquoJournal of Cancer Science and Therapy vol 5 no 10 pp 334ndash342 2013

[164] C O Omene J Wu and K Frenkel ldquoCaffeic Acid PhenethylEster (CAPE) derived from propolis a honeybee productinhibits growth of breast cancer stem cellsrdquo Investigational NewDrugs vol 30 no 4 pp 1279ndash1288 2012

[165] A M Alizadeh H Afrouzan N Dinparast-Djadid et alldquoChemoprotection of MNNG-initiated gastric cancer in ratsusing Iranian propolisrdquoArchives of IranianMedicine vol 18 no1 pp 18ndash23 2015

[166] E Szliszka Z P Czuba J Bronikowska A Mertas A Paradyszand W Krol ldquoEthanolic extract of propolis augments TRAIL-induced apoptotic death in prostate cancer cellsrdquo Evidence-Based Complementary and Alternative Medicine vol 2011Article ID 535172 11 pages 2011

[167] E Szliszka G Zydowicz B Janoszka C Dobosz G Kowalczyk-Ziomek and W Krol ldquoEthanolic extract of Brazilian greenpropolis sensitizes prostate cancer cells to TRAIL-inducedapoptosisrdquo International Journal of Oncology vol 38 no 4 pp941ndash953 2011

[168] E Szliszka and W Krol ldquoPolyphenols isolated from propolisaugment TRAIL-induced apoptosis in cancer cellsrdquo Evidence-Based Complementary and Alternative Medicine vol 2013Article ID 731940 10 pages 2013

[169] E Szliszka G Zydowicz E Mizgala and W Krol ldquoArtepillinC (35-diprenyl-4-hydroxycinnamic acid) sensitizes LNCaP

prostate cancer cells to TRAIL-induced apoptosisrdquo Interna-tional Journal of Oncology vol 41 no 3 pp 818ndash828 2012

[170] K McEleny R Coffey C Morrissey J M Fitzpatrick and RW G Watson ldquoCaffeic acid phenethyl ester-induced PC-3 cellapoptosis is caspase-dependent and mediated through the lossof inhibitors of apoptosis proteinsrdquo BJU International vol 94no 3 pp 402ndash406 2004

[171] V Cavaliere D L Papademetrio T Lombardo S NCostantino G A Blanco and E M C Alvarez ldquoCaffeicacid phenylethyl ester and MG132 two novel nonconventionalchemotherapeutic agents induce apoptosis of human leukemiccells by disrupting mitochondrial functionrdquo Targeted Oncologyvol 9 no 1 pp 25ndash42 2014

[172] K W Lee N J Kang J H Kim et al ldquoCaffeic acid phenethylester inhibits invasion and expression of matrix metallopro-teinase in SK-Hep1 human hepatocellular carcinoma cells bytargeting nuclear factor kappa Brdquo Genes and Nutrition vol 2no 4 pp 319ndash322 2008

[173] P Saharinen L Eklund K Pulkki P Bono and K AlitaloldquoVEGF and angiopoietin signaling in tumor angiogenesis andmetastasisrdquo Trends in Molecular Medicine vol 17 no 7 pp 347ndash362 2011

[174] M-R Ahn K Kunimasa T Ohta et al ldquoSuppression of tumor-induced angiogenesis by Brazilian propolis major componentartepillin C inhibits in vitro tube formation and endothelial cellproliferationrdquo Cancer Letters vol 252 no 2 pp 235ndash243 2007

[175] T Ohta K Kunimasa M-R Ahn et al ldquoBrazilian propo-lis suppresses angiogenesis by inducing apoptosis in tube-forming endothelial cells through inactivation of survival sig-nal ERK12rdquo Evidence-Based Complementary and AlternativeMedicine vol 2011 Article ID 870753 8 pages 2011

[176] S S Yun E H Park J J Kyung and C Jin ldquoInhibition ofangiogenesis by propolisrdquo Archives of Pharmacal Research vol25 no 4 pp 500ndash504 2002

[177] T Ohta K Kunimasa T Kobayashi M Sakamoto and K KajildquoPropolis suppresses tumor angiogenesis by inducing apoptosisin tube-forming endothelial cellsrdquoBioscience Biotechnology andBiochemistry vol 72 no 9 pp 2436ndash2440 2008

[178] M Keshavarz A Mostafaie K Mansouri Y Shakiba and HR M Motlagh ldquoInhibition of corneal neovascularization withpropolis extractrdquoArchives of Medical Research vol 40 no 1 pp59ndash61 2009

[179] H Izuta M Shimazawa K Tsuruma Y Araki S Mishima andH Hara ldquoBee products prevent VEGF-induced angiogenesis inhuman umbilical vein endothelial cellsrdquo BMC Complementaryand Alternative Medicine vol 9 article 45 2009

[180] V A Isidorov L Szczepaniak and S Bakier ldquoRapid GCMSdetermination of botanical precursors of eurasian propolisrdquoFood Chemistry vol 142 pp 101ndash106 2014

[181] S D Leonhardt H M Wallace and T Schmitt ldquoThe cuticularprofiles of Australian stingless bees are shaped by resin of theeucalypt tree Corymbia torellianardquo Austral Ecology vol 36 no5 pp 537ndash543 2011

[182] R Christov V Bankova I Tsvetkova A Kujumgiev and ADelgado Tejera ldquoAntibacterial furofuran lignans from CanaryIslands propolisrdquo Fitoterapia vol 70 no 1 pp 89ndash92 1999

[183] J F Campos U P dos Santos L F B Macorini et alldquoAntimicrobial antioxidant and cytotoxic activities of propolisfrom Melipona orbignyi (Hymenoptera Apidae)rdquo Food andChemical Toxicology vol 65 pp 374ndash380 2014


[184] A Mavri H Abramovic T Polak et al ldquoChemical propertiesand antioxidant and antimicrobial activities of Slovenian propo-lisrdquoChemistry and Biodiversity vol 9 no 8 pp 1545ndash1558 2012

[185] A A Lopes T S Ferreira R T Nesi et al ldquoAntioxidant actionof propolis on mouse lungs exposed to short-term cigarettesmokerdquo Bioorganic and Medicinal Chemistry vol 21 no 24 pp7570ndash7577 2013

[186] Y Aliyazicioglu S Demir I Turan et al ldquoPreventive andprotective effects of turkish propolis on H

2O2-induced DNA

damage in foreskin fibroblast cell linesrdquo Acta Biologica Hungar-ica vol 62 no 4 pp 388ndash396 2011

[187] M E Yonar S M Yonar M S Ural S Silici andM DusukcanldquoProtective role of propolis in chlorpyrifos-induced changes inthe haematological parameters and the oxidativeantioxidativestatus ofCyprinus carpio carpiordquo Food and Chemical Toxicologyvol 50 no 8 pp 2703ndash2708 2012

[188] N Orsolic D Sirovina G Gajski V Garaj-Vrhovac MJazvinscak Jembrek and I Kosalec ldquoAssessment of DNA dam-age and lipid peroxidation in diabetic mice effects of propolisand epigallocatechin gallate (EGCG)rdquo Mutation Research vol757 no 1 pp 36ndash44 2013

[189] A Rossi R Longo A Russo F Borrelli and L SautebinldquoThe role of the phenethyl ester of caffeic acid (CAPE) inthe inhibition of rat lung cyclooxygenase activity by propolisrdquoFitoterapia vol 73 supplement 1 pp S30ndashS37 2002

[190] O Koksel A Ozdulger L Tamer et al ldquoEffects of caffeic acidphenethyl ester on lipopolysaccharide-induced lung injury inratsrdquo Pulmonary Pharmacology and Therapeutics vol 19 no 2pp 90ndash95 2006

[191] MMM Abdel-Latif H JWindle B S El Homasany K Sabraand D Kelleher ldquoCaffeic acid phenethyl ester modulates Heli-cobacter pylori-induced nuclear factor-kappa B and activatorprotein-1 expression in gastric epithelial cellsrdquo British Journalof Pharmacology vol 146 no 8 pp 1139ndash1147 2005

[192] F Missima A C Pagliarone C L Orsatti J P Araujo Jr and JM Sforcin ldquoThe Effect of propolis onTh1Th2 cytokine expres-sion and production by melanoma-bearing mice submitted tostressrdquo Phytotherapy Research vol 24 no 10 pp 1501ndash15072010

[193] B J Conti M C Bufalo M D A Golim V Bankova andJ M Sforcin ldquoCinnamic acid is partially involved in propolisimmunomodulatory action on human monocytesrdquo Evidence-based Complementary and Alternative Medicine vol 2013Article ID 109864 7 pages 2013

[194] G Girgin T Baydar M Ledochowski et al ldquoImmunomodu-latory effects of Turkish propolis changes in neopterin releaseand tryptophan degradationrdquo Immunobiology vol 214 no 2pp 129ndash134 2009

[195] J H Park J K Lee H S Kim et al ldquoImmunomodulatory effectof caffeic acid phenethyl ester in Balbc micerdquo InternationalImmunopharmacology vol 4 no 3 pp 429ndash436 2004

[196] S Nolkemper J Reichling K H Sensch and P SchnitzlerldquoMechanism of herpes simplex virus type 2 suppression bypropolis extractsrdquo Phytomedicine vol 17 no 2 pp 132ndash1382010

[197] V Bankova A Galabov D Antonova N Vilhelmova and BDi Perri ldquoChemical composition of Propolis Extract ACF andactivity against herpes simplex virusrdquoPhytomedicine vol 21 no11 pp 1432ndash1438 2014

[198] K Kuwata T Takemura T Urushisaki et al ldquo34-dicaffeoylquinic acid a major constituent of Brazilian propolis

increases TRAIL expression and extends the lifetimes ofmice infected with the influenza a virusrdquo Evidence-BasedComplementary and Alternative Medicine vol 2012 Article ID946867 7 pages 2012

[199] M P Popova I B Chinou I N Marekov and V S BankovaldquoTerpenes with antimicrobial activity from Cretan propolisrdquoPhytochemistry vol 70 no 10 pp 1262ndash1271 2009

[200] H F Santana A A T Barbosa S O Ferreira and H CMantovani ldquoBactericidal activity of ethanolic extracts of propo-lis against Staphylococcus aureus isolated from mastitic cowsrdquoWorld Journal of Microbiology and Biotechnology vol 28 no 2pp 485ndash491 2012

[201] L Netıkova P Bogusch and P Heneberg ldquoCzech ethanol-free propolis extract displays inhibitory activity against a broadspectrum of bacterial and fungal pathogensrdquo Journal of FoodScience vol 78 no 9 pp M1421ndashM1429 2013

[202] R D O Orsi J M Sforcin S R Cunha Funari A Fernandes Jrand V Bankova ldquoSynergistic effect of propolis and antibioticson the Salmonella typhirdquo Brazilian Journal of Microbiology vol37 no 2 pp 108ndash112 2006

[203] ROOrsi JM Sforcin S R C Funari andV Bankova ldquoEffectsof Brazilian and Bulgarian propolis on bactericidal activity ofmacrophages against Salmonella Typhimuriumrdquo InternationalImmunopharmacology vol 5 no 2 pp 359ndash368 2005

[204] Z Yildirim S Hacievliyagil N O Kutlu et al ldquoEffect of waterextract of Turkish propolis on tuberculosis infection in guinea-pigsrdquo Pharmacological Research vol 49 no 3 pp 287ndash2922004

[205] A R Khosravi H Shokri D Nikaein et al ldquoYeasts as importantagents of onychomycosis in vitro activity of propolis againstyeasts isolated from patients with nail infectionrdquo Journal ofAlternative and Complementary Medicine vol 19 no 1 pp 57ndash62 2013

[206] H C Kuo W H Kuo Y J Lee W L Lin F P Chou and T HTseng ldquoInhibitory effect of caffeic acid phenethyl ester on thegrowth of C6 glioma cells in vitro and in vivordquo Cancer Lettersvol 234 no 2 pp 199ndash208 2006

[207] Y-J Chen M-S Shiao M-L Hsu T-H Tsai and S-Y WangldquoEffect of caffeic acid phenethyl ester an antioxidant frompropolis on inducing apoptosis in human leukemic HL-60cellsrdquo Journal of Agricultural and Food Chemistry vol 49 no11 pp 5615ndash5619 2001

[208] Y Akao H Maruyama K Matsumoto et al ldquoCell growthinhibitory effect of cinnamic acid derivatives from propolis onhuman tumor cell linesrdquoBiological and Pharmaceutical Bulletinvol 26 no 7 pp 1057ndash1059 2003

[209] H Hattori K Okuda T Murase et al ldquoIsolation identificationand biological evaluation of HIF-1-modulating compoundsfromBrazilian green propolisrdquoBioorganic andMedicinal Chem-istry vol 19 no 18 pp 5392ndash5401 2011

[210] C A Dornelas F V Fechine-Jamacaru I L Albuquerque et alldquoAngiogenesis inhibition by green propolis and the angiogeniceffect of L-lysine on bladder cancer in ratsrdquo Acta CirurgicaBrasileira vol 27 no 8 pp 529ndash536 2012

[211] J B Daleprane T Schmid N Dehne et al ldquoSuppression ofhypoxia-inducible factor-1120572 contributes to the antiangiogenicactivity of red propolis polyphenols in human endothelial cellsrdquoJournal of Nutrition vol 142 no 3 pp 441ndash447 2012

[212] T Kamiya H Nishihara H Hara and T Adachi ldquoEthanolextract of Brazilian red propolis induces apoptosis in humanbreast cancer MCF-7 cells through endoplasmic reticulum


stressrdquo Journal of Agricultural and Food Chemistry vol 60 no44 pp 11065ndash11070 2012

[213] H-P Lin S S Jiang and C-P Chuu ldquoCaffeic acid phenethylester causes p21CIP1 induction Akt signaling reduction andgrowth inhibition in PC-3 human prostate cancer cellsrdquo PLoSONE vol 7 no 2 Article ID e31286 2012

[214] Y-Y Kuo H-P Lin C Huo et al ldquoCaffeic acid phenethyl estersuppresses proliferation and survival of TW26 human oralcancer cells via inhibition of akt signalingrdquo International Journalof Molecular Sciences vol 14 no 5 pp 8801ndash8817 2013

[215] H J Hwang H J Park H-J Chung et al ldquoInhibitory effects ofcaffeic acid phenethyl ester on cancer cell metastasis mediatedby the down-regulation of matrix metalloproteinase expressionin human HT1080 fibrosarcoma cellsrdquo Journal of NutritionalBiochemistry vol 17 no 5 pp 356ndash362 2006

[216] H Seda Vatansever K Sorkun S Ismet Deliloglu Gurhan etal ldquoPropolis from Turkey induces apoptosis through activatingcaspases in human breast carcinoma cell linesrdquoActaHistochem-ica vol 112 no 6 pp 546ndash556 2010

[217] M Watabe K Hishikawa A Takayanagi N Shimizu andT Nakaki ldquoCaffeic acid phenethyl ester induces apoptosis byinhibition of NFkappaB and activation of Fas in human breastcancer MCF-7 cellsrdquo The Journal of Biological Chemistry vol279 no 7 pp 6017ndash6026 2004

[218] I Valenca F Morais-Santos V Miranda-Goncalves A M Fer-reira C Almeida-Aguiar and F Baltazar ldquoPortuguese propolisdisturbs glycolytic metabolism of human colorectal cancer invitrordquo BMC Complementary and Alternative Medicine vol 13article 184 2013

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


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Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


green and red among others [5 7 12] In terms of chemicalcomposition it is generally composed of 50 resin 30wax 10 essential oils 5 pollen and 5 other substanceswhich includeminerals and organic compounds like phenolicacids (cinnamic and caffeic acid) or their esters flavonoids(flavones flavanones flavonols and dihydroflavonols chal-cones) terpenes aromatic aldehydes and alcohols fatty acidsstilbenes and 120573-steroids [8 9] Analysis of different samplesrevealed that propolis chemical composition is difficult tostandardize because it depends on different phytogeographiccharacteristics like vegetation season and environmentalconditions of the site of collection as bees select differentplants in different habitats for propolis production [6 8 9]

Several in vitro and in vivo studies have been describingthe plethora of biological activities and chemical profilesof propolis from different geographic origins This reviewhighlights published data about such works focusing on theantimicrobial anti-inflammatory antioxidant immunomod-ulatory and antitumor activities of different propolis types inorder to unravel the potential of this natural compound forthe development of new drugs

2 Use of Propolis in Ancientand Current Times

Propolis is not a new discovery Since beersquos domesticationmen explore its products to their own benefit and propolisone of the most important chemical weapons of bees is noexception having been employed extensively since almostimmemorial times [6 13 15ndash17] It is stated that propolis usedates back to ancient times at least to 300 BC where it wasused in folk medicine and other activities in many parts ofthe world [16] It was familiar to the Egyptians in particularby the priests who controlled medicine and chemistry andknew very well propolis antiputrefactive properties Theylearned from the bees the embalming capacity of propolis asthis natural product is used to perform the mummificationof corpses and prevent spread of infections The Greekand the Roman physicians also acknowledged the potentialof propolis by employing it in wound treatment as anantiseptic and cicatrizing agent and as mouth disinfectantThe Persians described propolis as a drug capable of actingagainst eczemas myalgia and rheumatism Populations ofthe new world like Incas also used propolis as an antipyreticagent

Between the 17th and 20th century this natural productbecame very popular in Europe In 1969 in the former Unionof Soviet Socialist Republics (USSR) the use of propolis wasaccepted in human and veterinary medicine with severalapplications including the treatment of tuberculosis wherethe regression of lung problems and recovery of appetitewere observed Also it was believed to cure some diseases infolk Georgian medicine During World War II (1939ndash1945)doctors used propolis to treat wounds [15ndash17] but only in1985 in Japan propolis was considered as very promising inpharmacology Before that propolis was considered a prod-uct without market value especially because its productionis low and affects honey production Nowadays propolisis an important product in alternative medicine in Japan

being widely imported from Brazil [18] In the 17th centurythe Italian Antonio Stradivari who is considered the mostsignificant and the greatest crafter of string instruments likeviolins used propolis as an ingredient in the varnish of hisinstruments Curiously such as in the 17th century propolisis currently used in rosin for stringed instruments and in therepair of accordions [16]

Propolis is one of the few natural products that main-tained popularity for a long time although it is not considereda therapeutic agent in conventional medicine Actually it iswidely used as a component in pharmaceutical and cosmeticproducts such as antiacne creams facial and body creamsointments and lotions and several formulations for oralhygiene [15 16] It is also used in some foods and beveragesor simply as food supplement or healthy drinks This namewas attributed to the drinks because it is thought that propolisimproves human health and prevents diseases such as heartdisease or diabetes among others [19]

3 Origin and Composition of Propolis

Propolis knowledge has registered an important evolutionover time due to exhaustive studies regarding its chem-ical composition and biological activities In the 60s itwas thought that despite its complexity propolis chemicalcomposition was more or less constant Nevertheless inthe following years analysis of a large number of samplesfrom different geographic origins revealed that chemicalcomposition of propolis is highly variable and also difficultto standardize because it depends on factors such as thevegetation season and environmental conditions of the siteof collection [6 8 9] Marcucci [7] and Bankova et al [10]registered more than 300 substances in propolis and recentreports showed the presence of compounds never mentionedbefore [12 17 20 21]

Generally the main constituents of propolis are resin andvolatiles which are substances obtained from a variety ofbotanical processes in different parts of plants and beeswaxsecreted by the bees [9] Typical compounds are summarizedin Table 1 As can be seen plant sources vary among thedifferent parts of the globe leading to panoply of compoundsIn a review on propolis standardization different resin typeswere proposed poplar propolis birch green red ldquoPacificrdquoand ldquoCanarianrdquo [9 12] Samples of poplar propolis (egfrom Europe North America New Zealand and temperatezones of Asia) are mainly composed of flavonoids phenolicacids and their esters [10 20 22] clearly different fromother propolis types (Table 1) Portuguese propolis despitesimilar to the ones found in European samples also containsnew methylated esterified and hydroxylated derivatives offlavonoids and pinocembrinpinobanksin derivatives con-taining a phenylpropanoic acid derivative moiety in theirstructure [20 21] Our group recently showed that propolisfrom Pereiro (district of Guarda Beira Alta) (Figure 1) has ahigh concentration of phenolic components [23]

Poplar-type propolis is undoubtedly themost studied onebut there are many other propolis types Recent studies haverevealed a new type of European propolis Mediterraneanpropolis This type of propolis is distinguished by the high












Table1Ch

aracteris

ticcompo

unds

ofprop

olisfro

mdifferent

geograph

icoriginsa

ndrespectiv

eplant

source

Geographico

rigin

Plantsou

rce

Typicalcon

stituents(m

aincompo

nents)

References

EuropeN

orth

AmericaNew

Zealandand

temperatezoneso

fAsia

Popu

lusspp

morep

redo

minantly

Pnigra

Pino

cembrinpinob



their

esters

[102022]

Brazil

Green

prop

olis

Baccharis

spppredo

minantly

Bdracun

culifolia

Prenylated

phenylprop

anoidspheno

licacidsprenylated

p-coum

aricacidsacetop

heno

nes


cidskaempferideiso

saku

ranetin

and

kaem

pferol

[9103233]

Redprop

olis


Form

onon

etinisoliq


edicarpin

andbiochaninA

[323435]

Russia

Betulasppm

ores

pecificallyB

verrucosaB

pend

ulaandB

pubescens

Cinn

amicacidsph

enylprop


ermaninrhamno

citrin

kaem


l[10180]

CubaV

enezuela

Clusiasppm

ores

pecificallyC

rosea

andC

minor

Polyiso

prenylated

benzop

heno

nesmores


exantho

chym

oland

guttiferone

E[936]

Mediterranean

Greece

Prob

ablyCo

nifer

spp

Flavon


isocupressic

pim

aricand

commun

icacidsiso

agatho

lal

agathadiolferrugino

l8-elem

eneandtotarol

[2425]

Switzerland

Ptre

mula

Benzylp-coum


enolicglycerides

liked

icou





[26]

Malta

Ferulaspp m

ostp

robablyFerula

commun


isocupressic

com

mun

icpim

aricand

imbricatoloica

cidtogether

with

totaroland

13-epitorulosal

[27]

Turkey

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativa

Pino

cembrinpinob

anksin

andits



likep


acidscinn

amylcinn

amateandethyloleate

arom

aticacid

esterssuch

asbenzylcinn

amatebenzenedicarbo

xylic

acid

andflavano

lssuch

asbenzop

yran

andchrysin

[28ndash30]

Algeria

Popu

lusspp

Cistu

sspp

Pino

cembrinpinob

anksin

andits

acetatechrysin

apigenin


sinladanein

galang

inn

aringenin

tectochrysinm

etho

xychrysin

prenyleste

rsof

caffeicacidsferulic

acids



clerod

ane

[2831]

Austr

alia

Apismellifera

Acaciaparadoxa

Xantho

rrho


bin


prenylated

cinn

amicacidsflavano

nesflavono

lschalcones

[39ndash

42181]

Stinglessb

eeTetra

gonu

lacarbonaria

Ctorellianatre

es(fr

uitresins)

Africa

Nigeria

Prob

ablyMschwe

infurthii

Isofl

avon

oidsprenylatediso

flavono

idsandstilbenoids

[54]

Kenya


such


xydiph

yllin

geranyl

stilbenesand

geranylflavon

macarangin

[50]

Cameroo

nCon


ofam

yrin


ids

[53]

Oman

Azadira

chta

indicaA

cacia

sppand

Mangifer

aindica


nessuchas

7-O-m

ethyl-8

-prenylnaringenin



etho

xyflavano

nechalco

nes

cardanolcardo

lsandanacardica

cids

[51]

Ethiop

iaProb

ablyAc

aciaspp

Triterpenoids

such

as120572-a



eoland120572-a

nd120573-lu

peyl

acetates

[52]

Thailand

Styrax

trees

Phenylallylflavanon

e(E)-cinn


[48]

TheP

acificr

egion

OkinawaHaw

aiiandTaiwan

Macaranga

tanariu

sPrenylflavono

idsmores

pecificallyiso

nymph

aeol-Bnym

phaeol-Anym

phaeol-Bnym

phaeol-C

prop


[43ndash45]

Indo

nesia

Myanm

arMangifer

aindica


artane-ty


flavano

nes

[4647]

Canary

Island

sUn

know

nFu

rofuranlignans

[49182]





2O2) the










Table2Antioxidant

activ

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Portug

al(Serra

deBo

rnes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Hum

anerythrocytes

Decreaseinlip

idperoxidatio

n[64]

Free

radicalscaveng

ing

[62]

Brazil

Prop

olisfro

mthes

tinglessb

eeMelipona

orbignyi

prob

ablypo

plar

tree

PEE

Hum

anerythrocytes

Free

radicalscaveng

inginhibitio

nof

hemolysisandlip

idperoxidatio

n[183]

Portugal(C

entral

Algarve)

European

prop

olisPopu

lus

nigra

PEE

PWE

andmethano

licextracts

Free

radicalsscavenging

chelatio

nof

metalions

[63]

Cuba

Redprop

olisC

rosea

Methano

licextract

Nem

oroson

eFree

radicalsscavenging

[36]

Slovenia

European

prop

olisPopu

lus

nigra

PEE

Strong

redu

cing

power

andabilityto

scavenge

freer

adicals

andmetalions

[184]

Romania

European

prop

olisPopu

lus

nigra

PEE

FemaleS

wiss

mice(UVB

expo

sure)

Decreaseinmalon

dialdehyde

levels

resto

ratio

nof

glutathion

eperoxidase

activ

ity[83]

Kang

aroo

Island

Austr

alianprop

olisAc

acia

paradoxa


Free

radicalscaveng

ing

[39]

China

European

prop

olisPopu

lus

nigra

Ethylacetateextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[81]

Algeria

Mediterranean

prop

olisPopu

lusspp

andCistu

sspp

Methano

licextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[31]

Urugu

ayEu

ropean

andgreen

prop

olisPopu

lusn

igra

andB

dracun

culifolia

PEE

Bovine

aorticendo

thelialcells

Inhibitio

nof

low-densitylip

oprotein

peroxidatio

nand

NADPH

oxidasea

ndincrease

innitricoxides

ynthase

[82]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

C57B

L6mice(acutelun

ginflammationcaused

bycigarette

smoke)

Normalizationof

nitritem

yeloperoxidase

levels

superoxide

dism

utasecatalaseand

glutathion

eperoxidasea

ctivity

and

redu

ctionof

glutathion

eoxidized

glutathion

eratio

and

malon

dialdehyde

levels

[185]

Turkey

Mediterranean

prop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

nea

sativa

PEE

Fibrob

lastcells

Decreaseo

fDNAdamageind

uced

byH

2O2

[186]

MaleW

istar

rats

DecreaseinCA

Tactiv

ityandMDAlevelsin

NOSinhibited

rats

[84]

Carps

(Cyprin

uscarpio)

Decreaseinmalon

dialdehyde

levels

superoxide

dism

utase

activ

ityandincrease

ofcatalase

andglutathion

eperoxidase

activ

ity[187]

Purchasedfro

mSigm

aAldric

hCo

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Free

radicalscaveng

inginhibitio

nof

xanthine

oxidasea

ctivity

andlip

idperoxidatio

n[85]

MaleW

istar

albino

rats

Maintenance

ofsuperoxide

dism

utasea

ctivitydecreaseo

fxanthine

oxidasea

ctivity

andmalon

dialdehyde

andnitric

oxidaselevels

[86]

Perip

heralblood

mon

onuclear

cells

from

cyclists

Redu

ctionof

hypertherm

ia-in


nnecrosis

superoxide

prod

uctio

nglutathion

edepletio

nand

intracellularsup

eroxide

[87]


Table3Anti-infl

ammatorymechanism

sinvestig

ated

with

prop

olis

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

PurchasedSigm

aAldric

hCo

Synthesiz

ed

Characteristic

ofEu

ropeanB

razilian


olis


narin

genin

CAPE

Periton

ealm

acroph

ages

Supp

ressionof

lipoxygenasep

athw

ayof

arachido

nica

cid

metabolism

CAPE

beingthem

ostp

otentm

odulator

ofthea

rachidon

icacid

cascade

[90]

Croatia

European

prop

olisPopu

lusn

igra

Water-solub

lederiv

atives

Swiss

albino

mice

Redu

ctionof

DNAdamageinperip

herallym

phocytes

[188]

PEE

MaleS

wiss

albino

mice

Supp

ressionof

functio

nalactivity

ofmacroph

ages

[104]

PurchasedSigm

aAldric

hCo

J774

macroph

agesM

ale

Wistar

rats

Invitro

andin

vivo

inhibitio

nof

cyclo

oxygenase1

and

cyclo

oxygenase2

activ

ity[91189]

MaleW

istar

albino

rats

Decreaseo

fpolym

orph

onuclear

neutroph

ilicleuko

cyte

infiltra

tionin

thelun

gstissues

[190]

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Gastricepith

elialcelllin

e(A

GS)H

pylori(str

ainNCT

C116

38)

Inhibitio

nof

Hpylori-ind

uced

NF-kB

andactiv

ator

protein

1-DNA-

bind

ingactiv

itypreventionof

IkB120572

degradationin

AGSandsupp

ressionof


ukin

8prod

uctio

n[191]

PurchasedWakoPu

reCh

emicalIndu

stries

Ltd

RAW2647macroph

ages

Decreaseo

fthe

prod

uctio

nof

interle

ukin-1120573m

onocyte

chem

oattractant

protein1andthep

rodu

ctionandexpressio

nof

tumor


[98]

MaleS

wiss

inbred

strainmice

Decreaseo

fcyclooxygenase2

expressio

nNF-120581Bactiv

ity

c-Jun-N-te

rminalkinaseinh

ibito

rofN

F-120581Bkinase

(IKK

)andinhibitoro

fNF-120581B(IkB

)pho

spho

rylatio

n[97]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

RAW2647macroph

ages

Dow

nregulationof

NF-120581B

p38mito

gen-activ

ated

protein

kinaseand

c-Jun-N-te

rminalkinase

[101]

PurchasedAc

ros

Organics

Characteristic

ofEu

ropeanB

razilian


olis

Caffeicacid

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Sprague-Daw

leyrats

Inhibitio

nof

carrageenan-indu

cedrath

indpawse

demaa

ndthec

hemotaxisof

human

polymorph

onuclear

leuk

ocytes

(PMNs)

[95]

Synthesiz

edCh

aracteristic

ofEu

ropean

type

prop

olis

CAPE

Polymorph

onuclear

leuk

ocytes

obtained

from

Hum

anbloo

dInhibitio

nof

5-lip

oxygenasea

ctivity

andarachido

nica

cid

release

[103]

Chile

European

prop

olispo

plar

trees

PEE

MaleC

F-1m

ice

Inhibitio

nof

NOreleaseb

ythem

acroph

ages

[102]

China

European

prop

olisPopu

lusn

igra

PEEandPW

EMaleICR

micea

ndmale

Wistar

rats

Inhibitio

nof

thea


nof

mon

onuclear

macroph

agesdecreasep

rosta

glandin-E2

(PGE2)

andnitric

oxide(NO)levels

[61]

Brazil

Green

prop

olisB

dracun

culifolia

PWE

Swiss

andBA

LBcmice

Decreaseinthen

umbero

fmacroph

ages

andneutroph

ils

inhibitio

nof

proinfl

ammatorycytokinesa

ndincrease


[99]

Redprop

olisDalbergia

ecastaphyllum

PEE

MaleW

istar

rats

Decreaseinrenalm

acroph

ageinfi

ltrationin

ratswith

chronic

kidn

eydisease

[100]

Nepal

Nepalesep

ropo

lisprobablyShorea

robu

staD

albergiasissooAc

acia

catechuandBo

mbaxcie

ba

PEE

3101584041015840-dihydroxy-4-

metho

xydalbergion

e4-etho

xydalbergion

cearoin

andchrysin

Bone

marrow-derived

mast

cells

(BMMC)

from

C57B

L6

mice

Inhibitin

gIL-6T

NF-120572and

IL-13gene

expressio

nin

BMMC

andalso

inhibitin

gthea

ctivationof

IKKleadingto

NF-120581B

inactiv

ation

[96]













Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik


expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig


CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep


fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep


ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph


ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]











Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



























Table1Ch

aracteris

ticcompo

unds

ofprop

olisfro

mdifferent

geograph

icoriginsa

ndrespectiv

eplant

source

Geographico

rigin

Plantsou

rce

Typicalcon

stituents(m

aincompo

nents)

References

EuropeN

orth

AmericaNew

Zealandand

temperatezoneso

fAsia

Popu

lusspp

morep

redo

minantly

Pnigra

Pino

cembrinpinob



their

esters

[102022]

Brazil

Green

prop

olis

Baccharis

spppredo

minantly

Bdracun

culifolia

Prenylated

phenylprop

anoidspheno

licacidsprenylated

p-coum

aricacidsacetop

heno

nes


cidskaempferideiso

saku

ranetin

and

kaem

pferol

[9103233]

Redprop

olis


Form

onon

etinisoliq


edicarpin

andbiochaninA

[323435]

Russia

Betulasppm

ores

pecificallyB

verrucosaB

pend

ulaandB

pubescens

Cinn

amicacidsph

enylprop


ermaninrhamno

citrin

kaem


l[10180]

CubaV

enezuela

Clusiasppm

ores

pecificallyC

rosea

andC

minor

Polyiso

prenylated

benzop

heno

nesmores


exantho

chym

oland

guttiferone

E[936]

Mediterranean

Greece

Prob

ablyCo

nifer

spp

Flavon


isocupressic

pim

aricand

commun

icacidsiso

agatho

lal

agathadiolferrugino

l8-elem

eneandtotarol

[2425]

Switzerland

Ptre

mula

Benzylp-coum


enolicglycerides

liked

icou





[26]

Malta

Ferulaspp m

ostp

robablyFerula

commun


isocupressic

com

mun

icpim

aricand

imbricatoloica

cidtogether

with

totaroland

13-epitorulosal

[27]

Turkey

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativa

Pino

cembrinpinob

anksin

andits



likep


acidscinn

amylcinn

amateandethyloleate

arom

aticacid

esterssuch

asbenzylcinn

amatebenzenedicarbo

xylic

acid

andflavano

lssuch

asbenzop

yran

andchrysin

[28ndash30]

Algeria

Popu

lusspp

Cistu

sspp

Pino

cembrinpinob

anksin

andits

acetatechrysin

apigenin


sinladanein

galang

inn

aringenin

tectochrysinm

etho

xychrysin

prenyleste

rsof

caffeicacidsferulic

acids



clerod

ane

[2831]

Austr

alia

Apismellifera

Acaciaparadoxa

Xantho

rrho


bin


prenylated

cinn

amicacidsflavano

nesflavono

lschalcones

[39ndash

42181]

Stinglessb

eeTetra

gonu

lacarbonaria

Ctorellianatre

es(fr

uitresins)

Africa

Nigeria

Prob

ablyMschwe

infurthii

Isofl

avon

oidsprenylatediso

flavono

idsandstilbenoids

[54]

Kenya


such


xydiph

yllin

geranyl

stilbenesand

geranylflavon

macarangin

[50]

Cameroo

nCon


ofam

yrin


ids

[53]

Oman

Azadira

chta

indicaA

cacia

sppand

Mangifer

aindica


nessuchas

7-O-m

ethyl-8

-prenylnaringenin



etho

xyflavano

nechalco

nes

cardanolcardo

lsandanacardica

cids

[51]

Ethiop

iaProb

ablyAc

aciaspp

Triterpenoids

such

as120572-a



eoland120572-a

nd120573-lu

peyl

acetates

[52]

Thailand

Styrax

trees

Phenylallylflavanon

e(E)-cinn


[48]

TheP

acificr

egion

OkinawaHaw

aiiandTaiwan

Macaranga

tanariu

sPrenylflavono

idsmores

pecificallyiso

nymph

aeol-Bnym

phaeol-Anym

phaeol-Bnym

phaeol-C

prop


[43ndash45]

Indo

nesia

Myanm

arMangifer

aindica


artane-ty


flavano

nes

[4647]

Canary

Island

sUn

know

nFu

rofuranlignans

[49182]





2O2) the










Table2Antioxidant

activ

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Portug

al(Serra

deBo

rnes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Hum

anerythrocytes

Decreaseinlip

idperoxidatio

n[64]

Free

radicalscaveng

ing

[62]

Brazil

Prop

olisfro

mthes

tinglessb

eeMelipona

orbignyi

prob

ablypo

plar

tree

PEE

Hum

anerythrocytes

Free

radicalscaveng

inginhibitio

nof

hemolysisandlip

idperoxidatio

n[183]

Portugal(C

entral

Algarve)

European

prop

olisPopu

lus

nigra

PEE

PWE

andmethano

licextracts

Free

radicalsscavenging

chelatio

nof

metalions

[63]

Cuba

Redprop

olisC

rosea

Methano

licextract

Nem

oroson

eFree

radicalsscavenging

[36]

Slovenia

European

prop

olisPopu

lus

nigra

PEE

Strong

redu

cing

power

andabilityto

scavenge

freer

adicals

andmetalions

[184]

Romania

European

prop

olisPopu

lus

nigra

PEE

FemaleS

wiss

mice(UVB

expo

sure)

Decreaseinmalon

dialdehyde

levels

resto

ratio

nof

glutathion

eperoxidase

activ

ity[83]

Kang

aroo

Island

Austr

alianprop

olisAc

acia

paradoxa


Free

radicalscaveng

ing

[39]

China

European

prop

olisPopu

lus

nigra

Ethylacetateextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[81]

Algeria

Mediterranean

prop

olisPopu

lusspp

andCistu

sspp

Methano

licextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[31]

Urugu

ayEu

ropean

andgreen

prop

olisPopu

lusn

igra

andB

dracun

culifolia

PEE

Bovine

aorticendo

thelialcells

Inhibitio

nof

low-densitylip

oprotein

peroxidatio

nand

NADPH

oxidasea

ndincrease

innitricoxides

ynthase

[82]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

C57B

L6mice(acutelun

ginflammationcaused

bycigarette

smoke)

Normalizationof

nitritem

yeloperoxidase

levels

superoxide

dism

utasecatalaseand

glutathion

eperoxidasea

ctivity

and

redu

ctionof

glutathion

eoxidized

glutathion

eratio

and

malon

dialdehyde

levels

[185]

Turkey

Mediterranean

prop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

nea

sativa

PEE

Fibrob

lastcells

Decreaseo

fDNAdamageind

uced

byH

2O2

[186]

MaleW

istar

rats

DecreaseinCA

Tactiv

ityandMDAlevelsin

NOSinhibited

rats

[84]

Carps

(Cyprin

uscarpio)

Decreaseinmalon

dialdehyde

levels

superoxide

dism

utase

activ

ityandincrease

ofcatalase

andglutathion

eperoxidase

activ

ity[187]

Purchasedfro

mSigm

aAldric

hCo

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Free

radicalscaveng

inginhibitio

nof

xanthine

oxidasea

ctivity

andlip

idperoxidatio

n[85]

MaleW

istar

albino

rats

Maintenance

ofsuperoxide

dism

utasea

ctivitydecreaseo

fxanthine

oxidasea

ctivity

andmalon

dialdehyde

andnitric

oxidaselevels

[86]

Perip

heralblood

mon

onuclear

cells

from

cyclists

Redu

ctionof

hypertherm

ia-in


nnecrosis

superoxide

prod

uctio

nglutathion

edepletio

nand

intracellularsup

eroxide

[87]


Table3Anti-infl

ammatorymechanism

sinvestig

ated

with

prop

olis

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

PurchasedSigm

aAldric

hCo

Synthesiz

ed

Characteristic

ofEu

ropeanB

razilian


olis


narin

genin

CAPE

Periton

ealm

acroph

ages

Supp

ressionof

lipoxygenasep

athw

ayof

arachido

nica

cid

metabolism

CAPE

beingthem

ostp

otentm

odulator

ofthea

rachidon

icacid

cascade

[90]

Croatia

European

prop

olisPopu

lusn

igra

Water-solub

lederiv

atives

Swiss

albino

mice

Redu

ctionof

DNAdamageinperip

herallym

phocytes

[188]

PEE

MaleS

wiss

albino

mice

Supp

ressionof

functio

nalactivity

ofmacroph

ages

[104]

PurchasedSigm

aAldric

hCo

J774

macroph

agesM

ale

Wistar

rats

Invitro

andin

vivo

inhibitio

nof

cyclo

oxygenase1

and

cyclo

oxygenase2

activ

ity[91189]

MaleW

istar

albino

rats

Decreaseo

fpolym

orph

onuclear

neutroph

ilicleuko

cyte

infiltra

tionin

thelun

gstissues

[190]

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Gastricepith

elialcelllin

e(A

GS)H

pylori(str

ainNCT

C116

38)

Inhibitio

nof

Hpylori-ind

uced

NF-kB

andactiv

ator

protein

1-DNA-

bind

ingactiv

itypreventionof

IkB120572

degradationin

AGSandsupp

ressionof


ukin

8prod

uctio

n[191]

PurchasedWakoPu

reCh

emicalIndu

stries

Ltd

RAW2647macroph

ages

Decreaseo

fthe

prod

uctio

nof

interle

ukin-1120573m

onocyte

chem

oattractant

protein1andthep

rodu

ctionandexpressio

nof

tumor


[98]

MaleS

wiss

inbred

strainmice

Decreaseo

fcyclooxygenase2

expressio

nNF-120581Bactiv

ity

c-Jun-N-te

rminalkinaseinh

ibito

rofN

F-120581Bkinase

(IKK

)andinhibitoro

fNF-120581B(IkB

)pho

spho

rylatio

n[97]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

RAW2647macroph

ages

Dow

nregulationof

NF-120581B

p38mito

gen-activ

ated

protein

kinaseand

c-Jun-N-te

rminalkinase

[101]

PurchasedAc

ros

Organics

Characteristic

ofEu

ropeanB

razilian


olis

Caffeicacid

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Sprague-Daw

leyrats

Inhibitio

nof

carrageenan-indu

cedrath

indpawse

demaa

ndthec

hemotaxisof

human

polymorph

onuclear

leuk

ocytes

(PMNs)

[95]

Synthesiz

edCh

aracteristic

ofEu

ropean

type

prop

olis

CAPE

Polymorph

onuclear

leuk

ocytes

obtained

from

Hum

anbloo

dInhibitio

nof

5-lip

oxygenasea

ctivity

andarachido

nica

cid

release

[103]

Chile

European

prop

olispo

plar

trees

PEE

MaleC

F-1m

ice

Inhibitio

nof

NOreleaseb

ythem

acroph

ages

[102]

China

European

prop

olisPopu

lusn

igra

PEEandPW

EMaleICR

micea

ndmale

Wistar

rats

Inhibitio

nof

thea


nof

mon

onuclear

macroph

agesdecreasep

rosta

glandin-E2

(PGE2)

andnitric

oxide(NO)levels

[61]

Brazil

Green

prop

olisB

dracun

culifolia

PWE

Swiss

andBA

LBcmice

Decreaseinthen

umbero

fmacroph

ages

andneutroph

ils

inhibitio

nof

proinfl

ammatorycytokinesa

ndincrease


[99]

Redprop

olisDalbergia

ecastaphyllum

PEE

MaleW

istar

rats

Decreaseinrenalm

acroph

ageinfi

ltrationin

ratswith

chronic

kidn

eydisease

[100]

Nepal

Nepalesep

ropo

lisprobablyShorea

robu

staD

albergiasissooAc

acia

catechuandBo

mbaxcie

ba

PEE

3101584041015840-dihydroxy-4-

metho

xydalbergion

e4-etho

xydalbergion

cearoin

andchrysin

Bone

marrow-derived

mast

cells

(BMMC)

from

C57B

L6

mice

Inhibitin

gIL-6T

NF-120572and

IL-13gene

expressio

nin

BMMC

andalso

inhibitin

gthea

ctivationof

IKKleadingto

NF-120581B

inactiv

ation

[96]













Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik


expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig


CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep


fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep


ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph


ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]











Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















2O2) the










Table2Antioxidant

activ

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Portug

al(Serra

deBo

rnes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Hum

anerythrocytes

Decreaseinlip

idperoxidatio

n[64]

Free

radicalscaveng

ing

[62]

Brazil

Prop

olisfro

mthes

tinglessb

eeMelipona

orbignyi

prob

ablypo

plar

tree

PEE

Hum

anerythrocytes

Free

radicalscaveng

inginhibitio

nof

hemolysisandlip

idperoxidatio

n[183]

Portugal(C

entral

Algarve)

European

prop

olisPopu

lus

nigra

PEE

PWE

andmethano

licextracts

Free

radicalsscavenging

chelatio

nof

metalions

[63]

Cuba

Redprop

olisC

rosea

Methano

licextract

Nem

oroson

eFree

radicalsscavenging

[36]

Slovenia

European

prop

olisPopu

lus

nigra

PEE

Strong

redu

cing

power

andabilityto

scavenge

freer

adicals

andmetalions

[184]

Romania

European

prop

olisPopu

lus

nigra

PEE

FemaleS

wiss

mice(UVB

expo

sure)

Decreaseinmalon

dialdehyde

levels

resto

ratio

nof

glutathion

eperoxidase

activ

ity[83]

Kang

aroo

Island

Austr

alianprop

olisAc

acia

paradoxa


Free

radicalscaveng

ing

[39]

China

European

prop

olisPopu

lus

nigra

Ethylacetateextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[81]

Algeria

Mediterranean

prop

olisPopu

lusspp

andCistu

sspp

Methano

licextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[31]

Urugu

ayEu

ropean

andgreen

prop

olisPopu

lusn

igra

andB

dracun

culifolia

PEE

Bovine

aorticendo

thelialcells

Inhibitio

nof

low-densitylip

oprotein

peroxidatio

nand

NADPH

oxidasea

ndincrease

innitricoxides

ynthase

[82]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

C57B

L6mice(acutelun

ginflammationcaused

bycigarette

smoke)

Normalizationof

nitritem

yeloperoxidase

levels

superoxide

dism

utasecatalaseand

glutathion

eperoxidasea

ctivity

and

redu

ctionof

glutathion

eoxidized

glutathion

eratio

and

malon

dialdehyde

levels

[185]

Turkey

Mediterranean

prop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

nea

sativa

PEE

Fibrob

lastcells

Decreaseo

fDNAdamageind

uced

byH

2O2

[186]

MaleW

istar

rats

DecreaseinCA

Tactiv

ityandMDAlevelsin

NOSinhibited

rats

[84]

Carps

(Cyprin

uscarpio)

Decreaseinmalon

dialdehyde

levels

superoxide

dism

utase

activ

ityandincrease

ofcatalase

andglutathion

eperoxidase

activ

ity[187]

Purchasedfro

mSigm

aAldric

hCo

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Free

radicalscaveng

inginhibitio

nof

xanthine

oxidasea

ctivity

andlip

idperoxidatio

n[85]

MaleW

istar

albino

rats

Maintenance

ofsuperoxide

dism

utasea

ctivitydecreaseo

fxanthine

oxidasea

ctivity

andmalon

dialdehyde

andnitric

oxidaselevels

[86]

Perip

heralblood

mon

onuclear

cells

from

cyclists

Redu

ctionof

hypertherm

ia-in


nnecrosis

superoxide

prod

uctio

nglutathion

edepletio

nand

intracellularsup

eroxide

[87]


Table3Anti-infl

ammatorymechanism

sinvestig

ated

with

prop

olis

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

PurchasedSigm

aAldric

hCo

Synthesiz

ed

Characteristic

ofEu

ropeanB

razilian


olis


narin

genin

CAPE

Periton

ealm

acroph

ages

Supp

ressionof

lipoxygenasep

athw

ayof

arachido

nica

cid

metabolism

CAPE

beingthem

ostp

otentm

odulator

ofthea

rachidon

icacid

cascade

[90]

Croatia

European

prop

olisPopu

lusn

igra

Water-solub

lederiv

atives

Swiss

albino

mice

Redu

ctionof

DNAdamageinperip

herallym

phocytes

[188]

PEE

MaleS

wiss

albino

mice

Supp

ressionof

functio

nalactivity

ofmacroph

ages

[104]

PurchasedSigm

aAldric

hCo

J774

macroph

agesM

ale

Wistar

rats

Invitro

andin

vivo

inhibitio

nof

cyclo

oxygenase1

and

cyclo

oxygenase2

activ

ity[91189]

MaleW

istar

albino

rats

Decreaseo

fpolym

orph

onuclear

neutroph

ilicleuko

cyte

infiltra

tionin

thelun

gstissues

[190]

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Gastricepith

elialcelllin

e(A

GS)H

pylori(str

ainNCT

C116

38)

Inhibitio

nof

Hpylori-ind

uced

NF-kB

andactiv

ator

protein

1-DNA-

bind

ingactiv

itypreventionof

IkB120572

degradationin

AGSandsupp

ressionof


ukin

8prod

uctio

n[191]

PurchasedWakoPu

reCh

emicalIndu

stries

Ltd

RAW2647macroph

ages

Decreaseo

fthe

prod

uctio

nof

interle

ukin-1120573m

onocyte

chem

oattractant

protein1andthep

rodu

ctionandexpressio

nof

tumor


[98]

MaleS

wiss

inbred

strainmice

Decreaseo

fcyclooxygenase2

expressio

nNF-120581Bactiv

ity

c-Jun-N-te

rminalkinaseinh

ibito

rofN

F-120581Bkinase

(IKK

)andinhibitoro

fNF-120581B(IkB

)pho

spho

rylatio

n[97]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

RAW2647macroph

ages

Dow

nregulationof

NF-120581B

p38mito

gen-activ

ated

protein

kinaseand

c-Jun-N-te

rminalkinase

[101]

PurchasedAc

ros

Organics

Characteristic

ofEu

ropeanB

razilian


olis

Caffeicacid

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Sprague-Daw

leyrats

Inhibitio

nof

carrageenan-indu

cedrath

indpawse

demaa

ndthec

hemotaxisof

human

polymorph

onuclear

leuk

ocytes

(PMNs)

[95]

Synthesiz

edCh

aracteristic

ofEu

ropean

type

prop

olis

CAPE

Polymorph

onuclear

leuk

ocytes

obtained

from

Hum

anbloo

dInhibitio

nof

5-lip

oxygenasea

ctivity

andarachido

nica

cid

release

[103]

Chile

European

prop

olispo

plar

trees

PEE

MaleC

F-1m

ice

Inhibitio

nof

NOreleaseb

ythem

acroph

ages

[102]

China

European

prop

olisPopu

lusn

igra

PEEandPW

EMaleICR

micea

ndmale

Wistar

rats

Inhibitio

nof

thea


nof

mon

onuclear

macroph

agesdecreasep

rosta

glandin-E2

(PGE2)

andnitric

oxide(NO)levels

[61]

Brazil

Green

prop

olisB

dracun

culifolia

PWE

Swiss

andBA

LBcmice

Decreaseinthen

umbero

fmacroph

ages

andneutroph

ils

inhibitio

nof

proinfl

ammatorycytokinesa

ndincrease


[99]

Redprop

olisDalbergia

ecastaphyllum

PEE

MaleW

istar

rats

Decreaseinrenalm

acroph

ageinfi

ltrationin

ratswith

chronic

kidn

eydisease

[100]

Nepal

Nepalesep

ropo

lisprobablyShorea

robu

staD

albergiasissooAc

acia

catechuandBo

mbaxcie

ba

PEE

3101584041015840-dihydroxy-4-

metho

xydalbergion

e4-etho

xydalbergion

cearoin

andchrysin

Bone

marrow-derived

mast

cells

(BMMC)

from

C57B

L6

mice

Inhibitin

gIL-6T

NF-120572and

IL-13gene

expressio

nin

BMMC

andalso

inhibitin

gthea

ctivationof

IKKleadingto

NF-120581B

inactiv

ation

[96]













Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik


expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig


CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep


fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep


ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph


ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]











Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Antioxidant

activ

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Portug

al(Serra

deBo

rnes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Hum

anerythrocytes

Decreaseinlip

idperoxidatio

n[64]

Free

radicalscaveng

ing

[62]

Brazil

Prop

olisfro

mthes

tinglessb

eeMelipona

orbignyi

prob

ablypo

plar

tree

PEE

Hum

anerythrocytes

Free

radicalscaveng

inginhibitio

nof

hemolysisandlip

idperoxidatio

n[183]

Portugal(C

entral

Algarve)

European

prop

olisPopu

lus

nigra

PEE

PWE

andmethano

licextracts

Free

radicalsscavenging

chelatio

nof

metalions

[63]

Cuba

Redprop

olisC

rosea

Methano

licextract

Nem

oroson

eFree

radicalsscavenging

[36]

Slovenia

European

prop

olisPopu

lus

nigra

PEE

Strong

redu

cing

power

andabilityto

scavenge

freer

adicals

andmetalions

[184]

Romania

European

prop

olisPopu

lus

nigra

PEE

FemaleS

wiss

mice(UVB

expo

sure)

Decreaseinmalon

dialdehyde

levels

resto

ratio

nof

glutathion

eperoxidase

activ

ity[83]

Kang

aroo

Island

Austr

alianprop

olisAc

acia

paradoxa


Free

radicalscaveng

ing

[39]

China

European

prop

olisPopu

lus

nigra

Ethylacetateextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[81]

Algeria

Mediterranean

prop

olisPopu

lusspp

andCistu

sspp

Methano

licextract

Free

radicalscaveng

ingandferricredu

cing

activ

ity[31]

Urugu

ayEu

ropean

andgreen

prop

olisPopu

lusn

igra

andB

dracun

culifolia

PEE

Bovine

aorticendo

thelialcells

Inhibitio

nof

low-densitylip

oprotein

peroxidatio

nand

NADPH

oxidasea

ndincrease

innitricoxides

ynthase

[82]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

C57B

L6mice(acutelun

ginflammationcaused

bycigarette

smoke)

Normalizationof

nitritem

yeloperoxidase

levels

superoxide

dism

utasecatalaseand

glutathion

eperoxidasea

ctivity

and

redu

ctionof

glutathion

eoxidized

glutathion

eratio

and

malon

dialdehyde

levels

[185]

Turkey

Mediterranean

prop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

nea

sativa

PEE

Fibrob

lastcells

Decreaseo

fDNAdamageind

uced

byH

2O2

[186]

MaleW

istar

rats

DecreaseinCA

Tactiv

ityandMDAlevelsin

NOSinhibited

rats

[84]

Carps

(Cyprin

uscarpio)

Decreaseinmalon

dialdehyde

levels

superoxide

dism

utase

activ

ityandincrease

ofcatalase

andglutathion

eperoxidase

activ

ity[187]

Purchasedfro

mSigm

aAldric

hCo

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Free

radicalscaveng

inginhibitio

nof

xanthine

oxidasea

ctivity

andlip

idperoxidatio

n[85]

MaleW

istar

albino

rats

Maintenance

ofsuperoxide

dism

utasea

ctivitydecreaseo

fxanthine

oxidasea

ctivity

andmalon

dialdehyde

andnitric

oxidaselevels

[86]

Perip

heralblood

mon

onuclear

cells

from

cyclists

Redu

ctionof

hypertherm

ia-in


nnecrosis

superoxide

prod

uctio

nglutathion

edepletio

nand

intracellularsup

eroxide

[87]


Table3Anti-infl

ammatorymechanism

sinvestig

ated

with

prop

olis

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

PurchasedSigm

aAldric

hCo

Synthesiz

ed

Characteristic

ofEu

ropeanB

razilian


olis


narin

genin

CAPE

Periton

ealm

acroph

ages

Supp

ressionof

lipoxygenasep

athw

ayof

arachido

nica

cid

metabolism

CAPE

beingthem

ostp

otentm

odulator

ofthea

rachidon

icacid

cascade

[90]

Croatia

European

prop

olisPopu

lusn

igra

Water-solub

lederiv

atives

Swiss

albino

mice

Redu

ctionof

DNAdamageinperip

herallym

phocytes

[188]

PEE

MaleS

wiss

albino

mice

Supp

ressionof

functio

nalactivity

ofmacroph

ages

[104]

PurchasedSigm

aAldric

hCo

J774

macroph

agesM

ale

Wistar

rats

Invitro

andin

vivo

inhibitio

nof

cyclo

oxygenase1

and

cyclo

oxygenase2

activ

ity[91189]

MaleW

istar

albino

rats

Decreaseo

fpolym

orph

onuclear

neutroph

ilicleuko

cyte

infiltra

tionin

thelun

gstissues

[190]

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Gastricepith

elialcelllin

e(A

GS)H

pylori(str

ainNCT

C116

38)

Inhibitio

nof

Hpylori-ind

uced

NF-kB

andactiv

ator

protein

1-DNA-

bind

ingactiv

itypreventionof

IkB120572

degradationin

AGSandsupp

ressionof


ukin

8prod

uctio

n[191]

PurchasedWakoPu

reCh

emicalIndu

stries

Ltd

RAW2647macroph

ages

Decreaseo

fthe

prod

uctio

nof

interle

ukin-1120573m

onocyte

chem

oattractant

protein1andthep

rodu

ctionandexpressio

nof

tumor


[98]

MaleS

wiss

inbred

strainmice

Decreaseo

fcyclooxygenase2

expressio

nNF-120581Bactiv

ity

c-Jun-N-te

rminalkinaseinh

ibito

rofN

F-120581Bkinase

(IKK

)andinhibitoro

fNF-120581B(IkB

)pho

spho

rylatio

n[97]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

RAW2647macroph

ages

Dow

nregulationof

NF-120581B

p38mito

gen-activ

ated

protein

kinaseand

c-Jun-N-te

rminalkinase

[101]

PurchasedAc

ros

Organics

Characteristic

ofEu

ropeanB

razilian


olis

Caffeicacid

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Sprague-Daw

leyrats

Inhibitio

nof

carrageenan-indu

cedrath

indpawse

demaa

ndthec

hemotaxisof

human

polymorph

onuclear

leuk

ocytes

(PMNs)

[95]

Synthesiz

edCh

aracteristic

ofEu

ropean

type

prop

olis

CAPE

Polymorph

onuclear

leuk

ocytes

obtained

from

Hum

anbloo

dInhibitio

nof

5-lip

oxygenasea

ctivity

andarachido

nica

cid

release

[103]

Chile

European

prop

olispo

plar

trees

PEE

MaleC

F-1m

ice

Inhibitio

nof

NOreleaseb

ythem

acroph

ages

[102]

China

European

prop

olisPopu

lusn

igra

PEEandPW

EMaleICR

micea

ndmale

Wistar

rats

Inhibitio

nof

thea


nof

mon

onuclear

macroph

agesdecreasep

rosta

glandin-E2

(PGE2)

andnitric

oxide(NO)levels

[61]

Brazil

Green

prop

olisB

dracun

culifolia

PWE

Swiss

andBA

LBcmice

Decreaseinthen

umbero

fmacroph

ages

andneutroph

ils

inhibitio

nof

proinfl

ammatorycytokinesa

ndincrease


[99]

Redprop

olisDalbergia

ecastaphyllum

PEE

MaleW

istar

rats

Decreaseinrenalm

acroph

ageinfi

ltrationin

ratswith

chronic

kidn

eydisease

[100]

Nepal

Nepalesep

ropo

lisprobablyShorea

robu

staD

albergiasissooAc

acia

catechuandBo

mbaxcie

ba

PEE

3101584041015840-dihydroxy-4-

metho

xydalbergion

e4-etho

xydalbergion

cearoin

andchrysin

Bone

marrow-derived

mast

cells

(BMMC)

from

C57B

L6

mice

Inhibitin

gIL-6T

NF-120572and

IL-13gene

expressio

nin

BMMC

andalso

inhibitin

gthea

ctivationof

IKKleadingto

NF-120581B

inactiv

ation

[96]













Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik


expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig


CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep


fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep


ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph


ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]











Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table3Anti-infl

ammatorymechanism

sinvestig

ated

with

prop

olis

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

PurchasedSigm

aAldric

hCo

Synthesiz

ed

Characteristic

ofEu

ropeanB

razilian


olis


narin

genin

CAPE

Periton

ealm

acroph

ages

Supp

ressionof

lipoxygenasep

athw

ayof

arachido

nica

cid

metabolism

CAPE

beingthem

ostp

otentm

odulator

ofthea

rachidon

icacid

cascade

[90]

Croatia

European

prop

olisPopu

lusn

igra

Water-solub

lederiv

atives

Swiss

albino

mice

Redu

ctionof

DNAdamageinperip

herallym

phocytes

[188]

PEE

MaleS

wiss

albino

mice

Supp

ressionof

functio

nalactivity

ofmacroph

ages

[104]

PurchasedSigm

aAldric

hCo

J774

macroph

agesM

ale

Wistar

rats

Invitro

andin

vivo

inhibitio

nof

cyclo

oxygenase1

and

cyclo

oxygenase2

activ

ity[91189]

MaleW

istar

albino

rats

Decreaseo

fpolym

orph

onuclear

neutroph

ilicleuko

cyte

infiltra

tionin

thelun

gstissues

[190]

Characteristic

ofEu

ropean

type

prop

olis

CAPE

Gastricepith

elialcelllin

e(A

GS)H

pylori(str

ainNCT

C116

38)

Inhibitio

nof

Hpylori-ind

uced

NF-kB

andactiv

ator

protein

1-DNA-

bind

ingactiv

itypreventionof

IkB120572

degradationin

AGSandsupp

ressionof


ukin

8prod

uctio

n[191]

PurchasedWakoPu

reCh

emicalIndu

stries

Ltd

RAW2647macroph

ages

Decreaseo

fthe

prod

uctio

nof

interle

ukin-1120573m

onocyte

chem

oattractant

protein1andthep

rodu

ctionandexpressio

nof

tumor


[98]

MaleS

wiss

inbred

strainmice

Decreaseo

fcyclooxygenase2

expressio

nNF-120581Bactiv

ity

c-Jun-N-te

rminalkinaseinh

ibito

rofN

F-120581Bkinase

(IKK

)andinhibitoro

fNF-120581B(IkB

)pho

spho

rylatio

n[97]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

RAW2647macroph

ages

Dow

nregulationof

NF-120581B

p38mito

gen-activ

ated

protein

kinaseand

c-Jun-N-te

rminalkinase

[101]

PurchasedAc

ros

Organics

Characteristic

ofEu

ropeanB

razilian


olis

Caffeicacid

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Sprague-Daw

leyrats

Inhibitio

nof

carrageenan-indu

cedrath

indpawse

demaa

ndthec

hemotaxisof

human

polymorph

onuclear

leuk

ocytes

(PMNs)

[95]

Synthesiz

edCh

aracteristic

ofEu

ropean

type

prop

olis

CAPE

Polymorph

onuclear

leuk

ocytes

obtained

from

Hum

anbloo

dInhibitio

nof

5-lip

oxygenasea

ctivity

andarachido

nica

cid

release

[103]

Chile

European

prop

olispo

plar

trees

PEE

MaleC

F-1m

ice

Inhibitio

nof

NOreleaseb

ythem

acroph

ages

[102]

China

European

prop

olisPopu

lusn

igra

PEEandPW

EMaleICR

micea

ndmale

Wistar

rats

Inhibitio

nof

thea


nof

mon

onuclear

macroph

agesdecreasep

rosta

glandin-E2

(PGE2)

andnitric

oxide(NO)levels

[61]

Brazil

Green

prop

olisB

dracun

culifolia

PWE

Swiss

andBA

LBcmice

Decreaseinthen

umbero

fmacroph

ages

andneutroph

ils

inhibitio

nof

proinfl

ammatorycytokinesa

ndincrease


[99]

Redprop

olisDalbergia

ecastaphyllum

PEE

MaleW

istar

rats

Decreaseinrenalm

acroph

ageinfi

ltrationin

ratswith

chronic

kidn

eydisease

[100]

Nepal

Nepalesep

ropo

lisprobablyShorea

robu

staD

albergiasissooAc

acia

catechuandBo

mbaxcie

ba

PEE

3101584041015840-dihydroxy-4-

metho

xydalbergion

e4-etho

xydalbergion

cearoin

andchrysin

Bone

marrow-derived

mast

cells

(BMMC)

from

C57B

L6

mice

Inhibitin

gIL-6T

NF-120572and

IL-13gene

expressio

nin

BMMC

andalso

inhibitin

gthea

ctivationof

IKKleadingto

NF-120581B

inactiv

ation

[96]













Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik


expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig


CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep


fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep


ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph


ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]











Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




























Table4Im

mun

omod

ulatoryactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

MaleB

ALB

cmice

Upregulationof

toll-lik


expressio

nand

increasesininterle

ukin-1andinterle

ukin-6

prod

uctio

n[105]

Upregulationof

toll-lik


mRN

Aexpressio

n[111]

MaleC

57BL

6miceB16F

10cell

line

Stim

ulationof

thee

xpressionandprod

uctio

nof

interle

ukin-2

and

interle

ukin-10andTh

1cytokine(interle

ukin-2

andIFN-120574)p

rodu

ction

[192]

MaleB

ALB

cmice

Inhibitio

nof

Th1cellsgeneratio

nredu

ctionof

thefrequ

ency

ofIFN-120574-produ

cing

CD4+

Tcells

underTh

1-polarizingcond

ition

s[118]

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecreasesintheN

Ogeneratio

nin

periton

ealm

acroph

ages

[109]

MaleB

ALB

cmice

Increase

intheinterioriz

ationandkilling

ofthep

arasitesL

eishm

ania

(Viann

ia)b

raziliensisby

macroph

agesincreaseinTN

F-120572prod

uctio

nanddecrease

ininterle

ukin-12prod

uctio

n[117]

Mon

ocytes

from

human

bloo

dTL

R-4andCD

80expressio

nin

human

mon

ocytes

aswellasT

NF-120572

andIL-10prod

uctio

n[113]

Mela

nomac

ells(B16F10)m

ale

C57B

L6mice

Redu

ctionof

IL-1120573andIL-6

inLP

S-str

essedmiceindu

ctionof

IL-1120573

andIL-6

andTh

1cytok

ines

inmela

noma-bearingmices

ubmitted

orno

ttochronics

tress

[115]

Brazil

PurchasedAc

rosO

rganics

Green

prop

olisB

dracun

culifolia

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

PEE

cinn

amicandcoum

aricacids

MaleB

ALB

cmice

Stim

ulationof

interle

ukin-1120573prod

uctio

nandinhibitio

nof

interle

ukin-6

andinterle

ukin-10prod

uctio

ns[116]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

and

Mediterraneanprop

olis

Caffeicacid

Mon

ocytes

from

human

bloo

dStim

ulationof

mon

ocytes

activ

ityagainstC

albica

nsdow

nregulation

ofTL

R-2andHLA

-DRexpressio

nandinhibitio

nof

cytokine

prod

uctio

n[114]

PurchasedAc

rosO

rganics

Characteris

ticof

EuropeanB

razilian

Russian

Mediterranean

andAu

stralian

type

prop

olis

Cinn

amicacid

Mon

ocytes

from

human

bloo

dDow

nregulationof

toll-lik

ereceptor-2HLA

-DRmolecules

from

human

antig


CD80upregulationof

toll-lik

ereceptor-4inh

ibition

ofTN

F-120572andinterle

ukin-10prod

uctio

n[19

3]

PurchasedSigm

aAldric

hCo

Cinn

amicacid

FemaleIRC

mice

Increase

oflymph

ocytep


fcytok

ines

interle

ukin-1andinterle

ukin-2

[106]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Hydroalcoho

lic(H

PE)solution

MaleB

ALB

cmice

Increase

ofH

2O2generatio

nanddecrease

ofNOgeneratio

n[107]

MaleB

ALB

cmice

Decreaseo

fsplenocytep


ofIFN-120574

prod

uctio

nby

spleen

cells

[108]

Indo

nesia

TheP

acificr

egionprop

olisMacaranga

tanariu

sand

Mind

icaHPE

MaleB

ALB

cmice

Increase

ofIgGgeneratio

nandmacroph

agep

hagocytosis

activ

ityand

capacity

[110]

Turkey

Mediterraneanprop

olisPopu

lusspp

Eu

calyptus

sppand

Casta

neasativa

PEE

Perip

heralblood

mon

onuclear

cells

from

healthyhu

mans

Supp

ressionof

neop

terin

releasea

ndtryptoph

andegradation

downregulationof

thee

nzym

eind

oleamine2

3-dioxygenase

(IDO)and

decrease

ofIFN-120574

andTN

F-120572levels

[194]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

CAPE

Hum

anmon

ocyte-deriv

eddend

riticcells

(MoD

Cs)g

enerated

from

perip

heralm

onocytes

Inhibitio

nof

IL-12p4

0IL-12p70IL-10IFN-120574-in

duciblep

rotein-(IP-)

10levels

inhibitio

nof

I120581B120572

phosph


ation

[112]

FemaleB

ALB

cmice

Increase

ofIgM

antib

odyprod

uctio

nTlymph

ocytep

roliferation

interle

ukin-4

andinterle

ukin-2

prod

uctio

nby

spleno

cytesandIFN-120574

prod

uctio

n[195]

Hum

anperip

heralblood

mon

onuclear

cellsjurkatcells

Inhibitio

nof

transcrip

tionfactorsN

F-120581BandNFA

Tinhibitio

nof

interle

ukin-2

gene

transcrip

tion

interle

ukin-2

receptor

expressio

nand

proliferatio

nof

human

Tcells

[94]











Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























Table5Antivira

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescellsviru

ses

Effect

References

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

type

prop

olis

Caffeicacidp-cou

maricacid

benzoica

cidgalang

in

pino

cembrinand

chrysin

RC-37cellsherpessim

plex

virustype1

(HSV

-1)

strainKO

SHighanti-HSV

-1activ

ityforb


weretreated

prior

toviralinfectio

n[123]

CzechRe

public

European

prop

olisPopu

lusn

igra

PEEandPW

ERC

-37cellsherpessim

plex

virustype2

(HSV

-2)

Highantih

erpetic

activ

ityforb


ere

pretreated

priortoinfection

[196]

Brazil

Brow

nprop

olisB

dracun

culifolia

HPE

HSV

-2str

ainprop

agated

inVe

rocellsfem

aleB

ALB

cmice

Effectiv

eagainstHSV

-2infectionandin

redu

cing

extravaginallesio

nsby

actin

gon



especiestyrosin

enitration

ascorbicacid

levels

andmyeloperoxidase

activ

ityandprotectin

gagainstinh

ibition

ofcatalase

activ

ity

[124]

Characteris

ticof

Brazilian

prop

olis

Isop

entylferulate(

isolatedfro

man

PEE)

Influ

enza

virusesA

PR834

(H1N

1)

AKrasnod

ar10

159(H

2N2)and

AH

ongKo

ng168

(H3N

2)Supp

ressionof

influ

enza

virusA

Hon

gKo

ngreprod

uctio

nin

vitro

[121]

Green

prop

olisB

dracun

culifolia

Beriocla

daM

yrceugeniaeuosma

PEE

Influ

enza

APR834

(H1N

1)virusp

ropagated

Madin-D

arby

canine

kidn

ey(M

DCK

)cells

female

DBA

2Cr

mice

Redu

ctionof

body

weightlosso

finfectedmicea

ndvirusy

ieldsinthe

bron

choalveolarlavagefl

uids

oflung

s[122]

France

European

prop

olisPopu

lusn

igra

PEE

RC-37cellsH

SV-1str


mutantH

SV1-R

strainH29R

HSV

-2adeno

virustype

2po

liovirustype2

and

vesic

ular

stomatitisv

irus

(VSV

)

Redu

ctionof

titre

ofherpes

virusbeingvesic

ular

stomatitisv

irusa

ndadenoviru


cidalactionon

thee

nvelo

pedviruses

HSV

andVS

V[120]

Brazil

Geoprop

olisfro

mthes

tinglessb

eeScaptotrigona

postica

Hydromethano

licextract

African

greenmon

keykidn

eycells

(ATC

CCC

L-81)

herpes

simplex

virusstrain(M

cIntyre)

Inhibitio

nof

HSV


cells

[125]

Synthesiz

edCh

aracteris

ticof

Brazilian

redand

greenprop

olis

Hom

oisoflavono

idsspecially

3-benzyl-4-chrom

ones

BGM

(Buff

aloGreen

Mon

key)


B3B

4andA9andecho

virus3

0Goo

dantiv

iralactivity

againstthe

coxsackiev

irusesB

3B4

and

A9and

echo

virus3

0[126]

Canada

European

prop

olisPtrichocarpa

andPtre

muloides

PEE

HSV

-1andHSV

-2virusreplicated

inMDBK

(mon

olayer

cultu

reso

fMadin-D

arby

bovine

kidn

ey)

cells

Impairing

thea

bilityof

thev

irustoadsorb

orto

penetratethe

hostcells

[197]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia

Water

extracts

FemaleB

ALB

cmiceInflu

enza

Avirusstrain

AW

SN33(H

1N1)

Extensionof

thelifetim

eofm


cidwhich

increasesm

RNAlevelsof

tumor


apop

tosis

-indu

cing

anddecreasesH

1N1h

emagglutinin

mRN

A[19

8]Ch

aracteris

ticof

Brazilian

green

prop

olis


cid

(Isolated

from

Brazilian

prop

olis)

Brazil

Characteris

ticof

Brazilian

green

prop

olis

Melliferon

emoron

icacid

anwuw

eizonica

cidand

betulonica

cid(isolated

from

Brazilian

prop

olis)

H9lymph

ocytesH

IV-1

Moron

icacid

inhibitin

ganti-HIV

replication

[129]

Israel

Mediterraneanprop

olisPopu

lus

sppE

ucalyptusspp

andCa

stanea

sativa

PWE

Jurkatuninfectedhu

man

T-celllin

esand

MT2

(HTL

V-1infectedhu

man

Tcells)cells

Inhibitio

nof

thea

ctivationof

NF-120581B-depend

entp

romoter

byTaxand

preventio

nof

Taxbind

ingto

I120581B120572

andits

degradation

[127]

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Provided

byBinzho

uAnimal

Sciencea

ndVe

terin

ary

MedicineA

cademyof

Shando

ngProvince

Nanom

eter

prop

olisFlavon

eKidn

eycells

(PK-

15)

Porcinep

arvovirus(PP

V)

Britain

Whiteguinea

pigs

Inhibitio

nof

PPVinfectingpo

rcinek

idney-

(PK-

)15cells

Restr

aining

ofPP

Vcopy

inlung

gon

adand

bloo

ddecrease

ofthe

impactof

PPVon

weighto

fguineap

igsandincrease


nof

PPVin

serum


contentsof


[128]

USA

andCh

ina

European

prop

olisPopu

lusn

igra

PEE

Perip

heralblood

mon

onuclear

cells

obtained

from

bloo

dof

healthyd


latedfro

mhu

man

fetalbrain

tissueHIV-1ATH

IV-1SF162

Inhibitio

nof

HIV-1varia

ntse

xpression

[119]

Brazil

Green

prop

olisBa

ccharis

dracun

culifolia


Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table6Antibacteria

lactivity

ofprop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

PurchasedBe

eHealth

Ltd

(Scarborou

ghYorkshire

UK)

Eu

ropean

prop

olisPopu

lusn

igra

PEE

BsubtilisS

G38E

coliandR

sphaeroides

Influ

encing

theion

perm

eabilityof

theinn

erbacterial

mem

brane

Inhibitio

nof

bacterialm

otility

[130]

PurchasedSigm

aCh

emicalCo(Poo

leDorsetUK)

Characteris

ticof

EuropeanB

razilian


olis

CaffeicacidC

APE

qu

ercetin

and

narin

genin

Greece

Mediterraneanprop

olisprob

ablyCo

nifer

spp

Terpenes

(isolated

from

Cretan

prop

olis)

Saureus

(ATC

C25923)Sepiderm

idis(ATC

C12228)E

coli

(ATC

C25922)E

cloacae

(ATC

C13047)K

pneumoniae

(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Influ

encing

theG

ram-positive

andGram-negativeb

acteria

viability

[199]

France

European

prop

olisPopu

lusn

igra

Dichlorom

ethane

extract

Gram-negative7Ac

inetobacterb

aumannii(RC

HSAN00812

AYE

CIP7

034107292and

5377)2Escherich

iacoli(ATC

C25922andac

linicaliso

late)3

Pseudomonas

aeruginosa

(ATC


ofEn

terobacterclo

acaeE

aerogenesK

lebsiella

oxytocaand

Salm


type

4)Gram-negative13

Staphylococcus

aureus

(ATC

C25923six




clinicalisolates)2

clinicalisolates

ofS

epidermidis(m

ethiSandmethiR)3

clinicalisolates

ofEn

terococcus

faecalisand1E

faeciu

mand

1clin

icaliso

lateof

Corynebacterium

striatum

Influ

encing

theG

ram-positive


Saureus


and


le[133]

Bulgaria

Mediterraneanprop

olis

PEE

Saureus

209E

coliWF+

Decreaseo

fSaureusg

rowth

andweakor

lack

ofactiv

ityagainstE

coli

[28]

Greece

Popu

lusspp

Tu

rkey

Conifer

spp

Algeria

Popu

lusspp

Eu

calyptus

sppand

Casta

neasativaPopu

lusspp

Cistu

sspp

Austr

alia

Austr

alianprop

olisfro

msting

lessbee

Tetra

gonu


trees

(fruitresins)

PEE

Saureus

(ATC

C25923)

Paeruginosa

(ATC

C27853)

Inhibitio

nof

Saureus

grow

th[42]

Cameroo

nandCon

goAfrican

prop

olisprob

ablyM

schw

einfurthii

PEE

Saureus

(ATC

C25923)Sepiderm

is(ATC

C13047)E

coli

(ATC

C25922)K

lebsiella

pneumonia(ATC

C13883)and

Paeruginosa

(ATC

C227853)

Inhibitio

nof

Saureus

grow

th[53]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Saureus

2979

andSaureus

4118

isolated

from

mastiticcows

Saureus

(ATC

C29213)

Decreaseo

fSaureusg

rowth

incomplex

mediaandkilling

ofSaureus

cells

resuspendedin

milk

promotionof

changesin

morph

olog

yandcellsiz

e[200]

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsu

lfoxide

extract

Saureus

(CAPM

5970)E

faecalis(C

APM

5613

(EBF

3039))

Ecoli(C

AMP3101

T(U

541))and

Lmonocytogenes(C

CM5580)

Differentcon

centratio

nsaffectthe

grow


[201]

Italy

Mediterraneanprop

olisCrup

essusspp

PE

E

Staphylococcus

sppstr

ains


7S

hominis

18Shaem

olyticu

s10

Swa

rneri4Scapitisand

3S

auric

ularis)

andStreptococcusspp

strains

(59Sfaecalis

30S

virid

ans15

S120573-haemolyticu

sand19

Spn

eumoniae)

Com

pletes

uppressio

nof

thefactorc

oagu

lasereductio

nof

lipasea

ndpreventio

nof

biofi

lmform

ationof

Staphylococcus

increase

ofthee

ffectof

ampicillingentam

ycinand

streptomycin

andmod

eratingthea

ctionof

chloramph

enicol

ceftriaxoneand

vancom

ycin

[56]

Brazil

Redprop

olisDecasto

phyllum

Green

prop

olisB

dracun

culifolia

PEE

Saureus

(ATC

C25923)

NanoH

Amatrix

with

redandgreenprop

oliswhich

redu

ces

bacterialgrowth

andbiofi

lmform

ation

then

anoH

Awith

red

prop

olisbeingthem

ostefficient

[136]


Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table6Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Species

Effect

References

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lus

glutin

osaAe

sculus

hippocastanu

mFagus

sylva

tica

Coagu

lase-positive

Saureus

strains

isolatedfro

mbloo

dclinicalsam

plesSaureus(AT

CC25923)Saureus(AT

CC43300)m


andresistant

Saureus

Inhibitio

nof

Saureus

grow


ity

potentiatio

nof

antistaph

ylococcald

rugs

actio

neffectiv

eagainsttwelv

eSaureusstrainsw

ithMIC

values

with

in039

to078

mgmLandMBC

with

in078

to313mgmL

[132]

Brazil

Bulgaria

Green

prop

olisB

dracun

culifolia

Mediterraneanprop

olisPopu

lusspp

PEE

Styphi(00238)

Brazilian

prop

olishaving

bacteriosta

ticactiv

ityB

ulgaria

nprop

olishaving

bactericidalactiv

itybothhaving

similar

synergeticeffectw

henin

combinatio

nwith

amoxicillin

ampicillinandceph

alexin

[202]

Styphim

urium

MaleB

ALB

cmice

Increase

ofbactericidalactiv

ityof

macroph

ages

[203]

Styphim

urium

Both

samples

having

antib

acteria

lactivity

butn

osynergistic

effectswith

ciprofl

oxacinnorflo

xacin

andcotrim

oxazole

[135]

Turkey

Mediterran

eanpropolisPopu

lusspp

Eu

calyptus

sppan

dCa

staneasativa

PWE

Mtub

erculosis

(H37R v

)maleg

uinea-pig

Inhibitio

nof


guinea-pigssince

itprom

otes


ationandincrease

ingranulom

aformation

[204

]

PEE

Ecoli(ATC

C35218)K

pneum

oniae(AT

CC27736)P

aeruginosa

(ATC

C27853)M

organella

morganii(clinical

isolate)Saureus

(ATC

C25923)B

subtilis(ATC

C6633)and

Proteusv

ulgaris

Inhibitio

nof

Gram-negativeb

acteria

grow

th[134]

Purchasedfro

mSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

Hpylori

Com

petitiveinh

ibito

ragainstHpylorip

eptid

edeformylase

blocking

substratee

ntrance

[131]


Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table7Antifu

ngalactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

CalbicansC

tropicalisC

kruseiandC

guillier

mondiiadultvolun

teer

patie

ntssho

wing

symptom

sofstomatitis

Inhibitio

nof

cellgrow

thC

albica

nsbeingthem

ostsensitivea

ndC

guillier

mondiithe

mostresistantredu

ctionof

then

umbero

fCan

dida

yeastsin

thes

aliva

[141]

Green

prop

olisB

dracun

culifoliared

prop

olisDecasta

phyllum

PEE

Trubrum

TtonsuransTm

entagrophytesandT

mentagrophytes(AT

CC9533)(control)

Both

samples

which

decrease

cellgrow

thred

PEEbeingmoree

fficient

than

theg

reen

one

[143]

Green

prop

olisB

dracun

culifolia

PEE

PWE

matric

ial


ryextract

Calbicans

strains

SC5314

(wild

type)CA

I4and

3153A(w

ildtype)femaleB

ALB

cmice

PEEbeingthem

ostp

otentininhibitin

gcellgrow

thfollo

wed

byprop

olissolubled

ryextractprop

olismatric

ialm

icroparticlesandPW

EDifferentgelform

ulations

ofprop

olis

prop

olisbasedCa

rbop

ol940gel

(CP1)prop

olisbasedpo

loxamer

407gelw

ithCa

rbop

ol940(PP1)

prop

olisalginatewith

pectin

(AlP1

)andprop

olisbasedchito

sangel

with

Natrosol(Ch

P1)CP

1andchito

sangelsbeingthem

ost

pseudo

plastic

onespropo


gantifun

galaction

similartoclo

trim

azolec

ream

[150]

Green

prop

olisB

dracun

culifolia

PEE

gels

andcream

obtained

from

thee

xtract

Calbicans

strains

used

wereS

C5314CA

I4

BWP17DAY

2863153Aand

529L

(wild

type)

femaleB

ALB

cmice(murinem

odelof

vulvovaginalcand

idiasis

)

Indu

ctionof

celldeathin

Calbicans

mediatedviam

etacaspase

and

RASpathway

Inhibitio

nof

allthree

Calbicans

morph


utants


inthem

orph

ologicaltransitions

orin

the

maintenance

ofas

pecific

morph

otypew

hich

arem

ores

ensitiveto

prop

olis

Prop


which

werep

artia

llyableto

control

vulvovaginalcand

idiasis

[151]

Green

prop

olisB

dracun

culifolia

PEE

Calbicans

(ATC

C90028)29C

albicans

isolates

from

patie

ntsw

ithvulvovaginalcand

idiasis

Inhibitin

gbiofi

lmform

ationby

Calbicans

from

vulvovaginal

cand

idiasis

[149]

Redprop

olisDecasta

phyllum

n-Hexanee

xtract

5C

parapsilosis

(RL0

1RL

07R

L11RL

13and

RL27)5C

glabrata(RL0

3RL

09R

L12RL

34and

RL37)C

tropicalis

72Aand

Ckrusei(ATC

C6258)

Activ

eagainstflu

conazoleresistant

Cand

idaspp

[148]

France

European

prop

olisPopu

lusn

igra

PEE

PWE

methano

licextract

anddichloromethane

extract

Calbicans

(ATC

C66396)C

glabrata(LMA

90ndash1085)and

Afumigates(C

BS11326)

Antifu

ngalactiv

ityagainstC

albica

nsandC

glabratabu

tonlyhaving

aweakactiv

itytowards

Afumigates

[133]

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Pbrasiliensisperito

nealmacroph

ages

obtained

from

maleB

ALB

cmice

Increase

offung

icidalactiv

ityof

macroph

ages

againstPbrasilien

sis[14

2]Bu

lgaria

Mediterraneanprop

olisPopu

lusspp

CzechRe

public

European

prop

olisPopu

lusn

igra

Dim

ethylsulfoxide

extract

CalbicansA

fumigatusM

gypseum

and

M

canis

Affectingtheg

rowth


different

waysb

ydifferent

concentrations

[201]

Portugal(Bragancaa

ndLeiria)

European

prop

olisPopu

lusn

igra

PEE

CalbicansTrubrumand

Afumigatus

Plantextractsn

otexhibitin

grelevant

antifun

galactivitybut

ingeneral

both

prop

olissamples

affectin

gthefun

galgrowth

[140]

Poland

European

prop

olisPopu

lusn

igra

and

somes

pecies

ofBetulaalbaA

lnus

glutin

osaAe

sculus

hippocastanu

m

andFagussylv

atica

PEE

20iso

latedC

albicans14iso

latedC

glabrataand

10C

krusei

Inhibitio

nof

fung

algrow

th[14

7]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

CalbicansC

tropicalisC

kefyrC

kruseiM

globosaM

slooffi

aeand

Mpachyderm

atis

all

obtained

from

patie

ntsw


fon

ycho

mycosis

Decreaseo

fCan

dida

andMalasseziastr

ains

grow

thisolatedfro

mon

ycho

mycosis

even

inthefl

ucon

azole-resistant

strains

[205]


Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table7Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effectstim

ulus

References

Brazil

Green

prop

olisB

dracun

culifolia

PEEandprop

olismicroparticles

89yeaststrains

from

vaginalexu

dateso

fthe

vulvovaginalcand

idiasis

patie

nts58

Calbicans

and17

Cgla

brata1C

tropicalis8

Cguillier

mondiiand5C

parapsilosis

Inhibitio

nof

allyeasts

grow

thby

ethano

lextractandprop

olis

microparticleswith

smallvariatio

nindepend

ento

fthe

specieso

fyeast

[144]

Argentin

aTrop

icalregion

prop

olisSalix

humboldtia

naP

inus

sppE

ucalyptus

sppand

Popu

lusspp

PE

E

Xyloph

agou

s(G

applan

atum

Leleg

ansP

sanguineusand

Scommun

e)and

phytop

atho

genic(A

nigerFu

sariu

msp

Macrophom

inaspPnotatumand

Rhodotorula

spp)

Inhibitio

nof

fung

algrow

th[14

6]

Spain(Basqu

eCou

ntry)

European

prop

olisPopu

lusn

igra

PEEandprop

yleneg

lycol

extracts

Calbicans

(CEC

T1394)Scerevisia

e(CE

CT1383)

Inhibitio

nof

fung

algrow

th[14

5]




















Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



































Table8Antitu

moralactiv

ityof

prop

olisandits

chem

icalconstituents

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Thailand

Prop

olisfro

msting

lessbeeT

rigona

laevice

psHexanee

xtract

Colon

(SW620)breast(BT

474)hepatic

(Hep-G

2)lun

g(C

hago)andsto

mach(K

ato-III)

cells

Normalcelllin

esliver

(CH-liver)andfib

roblast

(HS-27)

Highantip

roliferativea

ctivity

againstthe

fivec

ancerc

elllines

andlow

cytotoxica

ctivity

onthen

ormalcelllin

es[5]

Poland

European

prop

olisPopu

lus

nigraandsome

specieso

fBetula

albaA

lnus

glutin

osaAe

sculus

hippocastanu

mand

Fagussylv

atica

PEE

Hum

anmalignant

melanom

acelllineM

e45

colorectalcancer

celllin

eHCT

116Inhibitio

nof

cellgrow

thandredu

ctionof

cellsiz

eofthe

teste

dcancer

cells

[154]

Synthesiz

ed

Characteris

ticof

prop

olisfro

mthe

Pacific

region

Th

ailand

Africa

Australiaand

Brazil

Prenylated

flavano

nes

Prostatecancer

celllin

esPC

-3andDU-145

Hum

anhepatomac

elllineH

ep-3B

Indu

ctionof

amorep

otentcytotoxicity

againstthe

PC-3

celllin

ethan

5-flu

rouracilindu

ctionof

apop

tosis

[45]

Characteris

ticof

European

prop

olis

CAPE

C6celllin

eesta

blish

edfro

mag

liomag

enerated

byintravenou

sexp

osureo

fmaleW

istar

ratsto

N-nitrosom

ethylureaB

ALB

c-numice

Inhibitio

nof

C6gliomac

ellsgrow

thincreaseinthep

ercentageo

fcellsin

the

G0G1p

haseand

decrease

inthep

rotein

levelofh

yperph

osph

orylated

pRb

increase

incyclindepend

entk

inaseinh

ibito


intumor

grow

thin

xeno

graft

sredu

ctionof

then

umbero

fmito

ticcells

and

proliferatin

gcellnu

clear

antig

en-(PC

NA-

)positive

cells

inC6

glioma

[206]

HL-60

celllin

eIndu

ctionof

apop

tosis

byactiv

ationof

caspase-3do

wnregulationof

Bcl-2

and

upregu

latio

nof

Bax

[207]

Brazil

Characteris

ticof

Brazilian

prop

olis

Drupanin

baccharin

((E)-3-prenyl-4

-(23-


cinn

amicacid)a


from

PEEs

ofprop

olis)

Hum

anleuk

emiacelllin

eHL-60colon

cancer

celllin

eSW480

Inhibitio

nof

cells

grow

thpromotionof

morph

ologicalchangesa

ndnu

cleosom

alDNAfragmentatio

n(artepillin

Cgtbaccharingtdrup

anin)

[208]

Redprop

olisD

ecastaphyllum

Methano

licextract

Hum

anpancreaticcancer

cells

(PANC-

1)Killing

100

ofPA

NC-

1cellsin

then

utrie

nt-depriv

edcond

ition

[157]

Green

prop

olisB

dracun

culifolia

PEE

DU145andPC

-3celllin

es

telomerase-im

mortalized

prim

aryhu

man


cell(RC-

58ThSA

4)

andprim

aryhu

man

prostateepith

elialcells

(PrEC)

Inhibitio

nof

human

prostatecancer

cells

proliferatio

nby

regu

latin

gthe

proteinexpressio

nof

cyclinD1B1

andcyclindepend

entk

inase(CD

K)p21

[158]

Green

prop

olisB

dracun

culifolia

Baccharin

beturetol

kaem

pferide

isosaku

ranetin

and

drup

anin

(isolated

from

PEE)

Hum

anem

bryonick

idney293(H

EK293)

cell

HCT

116celllin

e

Inhibitio

nof

HIF-1120572glucose

transporter1hexok

inase2

and

vascular

endo

thelialgrowth

factor

A(V

EGF-A)expression

exhibitin

ganti-angiogenic

effectsin

thec

hick

chorioallantoicm

embrane

[209]

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

scells

Indu

ctionof

apop

tosis

intube-fo

rmingendo

thelialcellsthroug

hthe

inactiv

ationof

thes

urvivalsignalE

RK12

andby

thea

ctivationof

caspase-3

[175]

Green

prop

olisB

dracun

culifolia

PWE

FemaleW

istar

rats

Inhibitio

nof

angiogenesisin


tyl)nitro

samine-

(BBN

-)indu

cedratb

ladd

ercancer

[210]

Redprop

olisD

ecastaphyllum

PEE

Hum

anim

mortalized

endo

thelial-likec

ellline


acelllineR

CC4

andmou

seem

bryonics

tem

celllin

eCGR

Redu

ctionof

migratio

nandsproutingof

endo

thelialcells

andattenu

ationof

newbloo

dvessels

form

ation

decrease

inthed

ifferentiatio

nof

embryonics

tem

cells

into

CD31

positivec

ells

decrease

inHIF1-120572


attenu

ates

VEG

Fgene

expressio

nincreasesthe

vonHippel-L

indau-

(pVHL-)

depend

entp

roteasom

aldegradationof

HIF1-120572

and

downregulates

Cdc42

proteinexpressio

n

[211]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Brazil

Green

prop

olisB

dracun

culifolia

PEE

Hum

anum

bilicalvein

endo

thelialcells

(HUVEC

s)N

F1-deficientM

PNST

(S-462)and


ma(

HEI-193)celllines

Femalen

unu

mice

Blocking

PAK1

signalin

gselectively

with

outaffectingAKT

sup

pressin

galmost

completely

theg

rowth

ofhu

man

neurofi

brom

atosistumor

xeno

graft

sinmice

[156]

Synthesiz

edCh

aracteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

HUVEC

sFemaleICR

mice

Redu

ctionof

then

umbero

fnew

lyform

edvessels

invivo

Supp

ressionof

HUVEC


nof

tube

form

ation

[174]

PurchasedWakoPu

reCh

emicalsInd

ustries

(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

C

Brazil

Green

prop

olisB

dracun

culifolia

PEE

LNCa

Pcelllin

e

Sensitizing

TRAIL-resistantL

NCa

Pcells

toTR

AIL-in

ducedapop

tosis

Indu

ctionof

asignificantd

isrup

tionof

ΔΨm

Enhancingthee

xpressionof


gthea

ctivity

ofNF-120581B

Artepillin

Cqu

ercetin

kaempferoland

p-coum

aricacid

stron

glycoop

erating

with

TRAIL

toindu

ceapop

tosis

[167]

PurchasedAlexis


CAU

SA)

Characteris

ticof

Brazilian

prop

olis


p-coum

aricacid

PurchasedWakoPu

reCh

emicals(OsakaJapan)

Artepillin

C

Brazil

Redprop

olisD

ecastaphyllum

PEE

MCF

-7celllin

eRe

ducing

cellviabilitythroug

hindu

ctionof

mito

chon

driald

ysfunctio

ncaspase-3activ

ityand

DNAfragmentatio

nandincrease

inexpressio

nof

CCAAT

enh

ancer-bind

ingproteinho

mologou

sprotein

(CHOP)

[212]

PurchasedAp

iCoLtd

Gifu

Japan

Characteris

ticof

European

prop

olis

CAPE

PurchasedSigm

aAldric

hCo

Characteris

ticof

European

prop

olis

CAPE

LNCa

P104-SDU-145and

PC-3

celllin

esMaleB

ALB

cmice

Supp

ressingtheg

rowth

ofLN

CaPDU-145and

PC-3

andinhibitin

gthetum

orgrow

thof

LNCa

Pxeno

graft

spo

ssibleinhibitio

nof

p70S6K

andsomeA

ktsig

nalin

gnetworks

[161]

PC-3

celllin

e

Supp

ressingproliferatio

ncolony

form

ation

andcellcycle

progression

decrease

inproteinexpressio

nof

cyclinD1cyclinE

SKP2

c-M

ycA

kt1Akt2

Akt3totalA

ktm

TOR

andBc

l-2R

bas

wellasp

hospho

rylationof

Rb

ERK1

2A

ktm

TOR

GSK

3aG

SK3band

PDK1

and

increase

inKL

F6and

p21C

ip1proteinexpressio

n

[213]

Breastcelllin

esMDA-

MB-231MCF

-7M

CF-10A

andMCF

-12A

Bovine

capillary

endo

thelial(BC

E)cells

Female(Ncr-nu-nu

)mice

Inhibitio

nof

invitro

andin

vivo

MCF

-7andMDA-

MB-231tum

orgrow

thwith

outm

ucheffecto

nno

rmalmam

marycellsind

uctio

nof

cellcycle

arrest

andapop

tosis

bydo

wnregulationof

Bcl-2

proteinsreductio

nof

NF-120581Band

mdr-1gene

expressio

nandsupp

ressionof

VEG

Fprod

uctio

nby

MDA-

231cells

andform

ationof

capillary-like

tubesb

yendo

thelialcells

[162]

Breastcancer

celllin

esMDA-

MB-231MCF

-7and

SKBR

3

Prom

otionof

anaccumulationof

acetylated

histo

neproteins

inMCF

-7(ER+

)andMDA-


Her2minus

)decrease

ofER

andPR

inMCF

-7cells

andup

regu

latio

nof

ERanddecrease

ofEG

FRin

MDA-

MB-231cells

redu

ction

ofHer2proteinin

SKBR

3(H

er2+

)cells

[163]

Hum

anoralsquamou

scellcarcino

maT

W26

Supp

ressionof

cellproliferatio

nandcolony

form

ation

decrease

ofG1p

hase

cellpo

pulatio

nincrease

ofG2M

phasec

ellp

opulation

indu

ctionof

apop

tosis

decreaseo

fAktA

kt1Akt2Akt3ph

osph

o-Akt

Ser473

phosph

o-Akt

Thr3

08G

SK3120573

FOXO

1FO

XO3apho

spho

-FOXO

1Thr24

phosph

o-Fo

xO3a

Thr32NF-120581B

phosph

o-NF-120581BSer536R

bph

osph

o-Rb

Ser807811

Skp2and

cyclinD1andincrease

ofcellcycle

inhibitorp

27Kip

[214]

MDA-

MB-231cellline

Inhibitio

nof

cancer

stem

cells


andclo

nal

grow

thanddecrease

ofCD

44levels

[164

]

Hum

anhepatocellu

larc

arcino

mac

ellline

SK-H

ep1

Supp

ressionof

thea

dhesionandinvasio

npo

tentialofthe

cells

byinhibitin

gcompletely

thee

xpressionof


(MMP-9)

and

theN

F-120581B

[172]

Hum

anfib

rosarcom

acelllineH

T1080

Decreaseo

fMMPandtissueinh

ibito


(TIM

P-2)

mRN

Alevels

downregulationof


ninhibitio

nof

MMP-2activ

itydecreaseo

finvasion

motilitycellm

igratio

nandcolony

form

ation

[215]


Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table8Con

tinued

Orig

inProp

olistypeplant

source

Type

ofextractisolated

compo

und(s)

Speciescells

Effect

References

Turkey

Mediterranean

prop

olisPopu

lus

sppE

ucalyptusspp

andCa

staneasativa

PEE

MCF

-7celllin

eIncrease

ofapop

tosis

throug

hthec

aspase

pathway

[216]

Iraq

European

prop

olisPopu

lus

nigra

PWE

HL-60

celllin

ecoloncancer

cellHCT

-116

Femalea

thym

icFo

xN1-n

unu

mice

Inhibitio

nof

HL-60

cells

proliferatio

nandindu

ctionof

apop

tosis

bydo

wnregulatingBc

l-2proteinandup

regu

latingBa

xinhibitio

nof

HCT

-116

cells

colony

form

ationpo

tentialand

prom

otionof


ofmito

ticcells

andincrease


nin

HCT

-116

tumor-bearin

gmice

[13]

Iran

European

prop

olisPoplar

spp

Ferulaovina

PEE

MaleW

istar

rats

Decreaseo

ftum

ourincidencenum

bero


ormalities

andbeta-catenin

andindu

ctionof

proapo

ptoticBa

xexpressio

nandredu

ction

ofantia

poptoticBc

l-2expressio

n[165]

Provided

byWakoPu

reCh

emicals(OsakaJapan)

Characteris

ticof

Brazilian

prop

olis

Artepillin

CLN

CaPcelllin

eIndu

ctionof


ationanddisrup

tionof

mito

chon

drialm

embranep

otentia

lbyac

otreatmentw

ithTR

AIL

and

artepillinC

[169]

Purchased

Characteris

ticof

European

prop

olis

CAPE

MCF

-7celllin

eIndu

ctionof

apop

tosis

viaF

assig

nalindu

ctionof

Baxproteinandactiv

ation

ofcaspases

andMAPK

family

proteins

p38andJN

K[217]

PurchasedCa

lbiochem

(San

DiegoC

AU

SA)

Characteris

ticof

European

prop

olis

CAPE

Lymph

oblasto

idcelllin

ePL104

Indu

ctionof

apop

tosis

throug

hph

osph

atidylserin

e(PS

)exp

osurea

ndnu

clear

fragmentatio

nIncrease

ofsub-G1D

NAcontentdo

wnregulationof

survivingandBc

l-2expressio

nandincrease

ofBA

Xproteins

levels

indu

ctionof

mito

chon

drial

mem

branep

otentia


ctionof

cytochromec

releasefrom

mito

chon

driaandindu

ctionof

caspases

37and9activ

ation

[171]

China

European

prop

olisPopu

lus

nigra

PEE

HUVEC

sInhibitio

nof

VEG

Fexpressio

n[179]

PurchasedAp

iCoLtd

(Gifu

Japan)

Characteris

ticof

European

prop

olis

CAPE

Korea

European

prop

olisPopu

lus

nigra

PEE


Calfpu

lmon

aryarteria

lend

othelial(CP

AE)

cells

Inhibitio

nof

angiogenesisin

chickem

bryo

chorioallantoicm

embranea

ndinhibitio

nof

CPAEcells

proliferatio

n[176]

Synthesiz

edCh

aracteris

ticof

European

prop

olis

CAPE

Portugal(Serrad

eBornes

andFu

ndao)

European

prop

olisPopu

lus

nigra

Methano

licextract

Normalandcancerou

srenalcells

deriv

edfro

mhu

man

renalcellcarcino

map

atientshu

man

renal

carcinom

acelllineA

-498

Inhibitio

ntumor

cells

grow

thexhibitin

gselectivetoxicity

againstm

alignant

cells

comparedto

norm

alcells

[64]

(Ang

adoHeroısm

oAzores)

PEEandhexane

chloroform

and

resid

ual

ethano

lextractfractio

nsob

tained

from

theP

EE

Hum


mac

ellline

HCT

-15

Allthes

amples

exhibitin

gcytotoxice

ffectagainsttum

orcellschloroform

fractio

ndecreasin


rbingtumor


[218]






5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















5 Conclusions



Abbreviations




References






































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















































































































































































































2O2-induced DNA










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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