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Review Article Lippia javanica (Burm.f.) Spreng.: Traditional and Commercial Uses and Phytochemical and Pharmacological Significance in the African and Indian Subcontinent Alfred Maroyi Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa Correspondence should be addressed to Alfred Maroyi; [email protected] Received 5 September 2016; Revised 25 October 2016; Accepted 20 November 2016; Published 1 January 2017 Academic Editor: Rainer W. Bussmann Copyright © 2017 Alfred Maroyi. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Lippia javanica occurs naturally in central, eastern, and southern Africa and has also been recorded in the tropical Indian subcontinent. e potential of L. javanica as herbal or recreational tea and herbal medicine and its associated phytochemistry and biological properties are reviewed. e extensive literature survey revealed that L. javanica is used as herbal tea and has ethnomedicinal applications such as in colds, cough, fever, malaria, wounds, diarrhoea, chest pains, bronchitis, and asthma. Multiple classes of phytochemicals including volatile and nonvolatile secondary metabolites such as alkaloids, amino acids, flavonoids, iridoids, and triterpenes as well as several minerals have been identified from L. javanica. Scientific studies on L. javanica indicate that it has a wide range of pharmacological activities which include anticancer, antiamoebic, antidiabetic, antimalarial, antimicrobial, antioxidant, antiplasmodial, and pesticidal effects. Although many of the traditional uses of L. javanica have been validated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved. Lippia javanica is popular as both herbal and recreational tea, but there is need for more precise studies to evaluate the safety and clinical value of its main active crude and pure compounds and to clarify their mechanisms of action. 1. Introduction Lippia javanica (Burm.f.) Spreng. (Verbenaceae) (Figure 1(a)) has a long history of traditional uses in tropical Africa as indigenous herbal tea or tisane (Figure 1(b)), refresh- ing beverage, or food additive based on its perceived health and medicinal properties. Lippia javanica is rich in volatile oil, particularly caryophyllene, carvone, ipsenone, ipsdienone, limonene, linalool, myrcene, myrcenone, oci- menone, p-cymene, piperitenone, sabinene, and tagetenone [1–5]. Research by Viljoen et al. [3] revealed that the essential oil profiles of L. javanica are characterized by inter- and intraspecies variations because they are produced by different metabolic pathways. Using cluster analysis, Viljoen et al. [3] identified five chemotypes of L. javanica in South Africa and Swaziland, myrcenone-rich type (36–62%), carvone-rich type (61–73%), piperitenone-rich type (32–48%), ipsdienone- rich type (42–61%), and linalool-rich type (>65%). e relative proportion of the chemical constituents of L. javanica essential oil is important as this determines the biological properties of the species chemotypes. Lippia javanica belongs to the Verbena or vervain family (Verbenaceae) comprising approximately 32 genera and 840 species [97]. e genus Lippia L. is named aſter Augustin Lippi (1678–1701), an Italian botanist and natural historian who was killed in Ethiopia at the age of 23 [98]. Phylogenetic relationships within family Verbenaceae demonstrated that genus Lippia and other closely related genera, namely, Aloysia Pal´ au, Lantana L., and Phyla Lour., are not monophyletic [97]. e boundaries separating these four genera are his- torically weak, with many taxonomic researchers including species belonging to Aloysia, Lantana, and Phyla in the genus Lippia [99]. Lippia and Lantana genera are the most difficult to separate, as species of these two genera show similarities in their inflorescences that are spicate, oſten subcapitate during anthesis and elongating in fruit and pedunculated Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2017, Article ID 6746071, 34 pages https://doi.org/10.1155/2017/6746071

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  • Review ArticleLippia javanica (Burm.f.) Spreng.: Traditional andCommercial Uses and Phytochemical and PharmacologicalSignificance in the African and Indian Subcontinent

    Alfred Maroyi

    Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa

    Correspondence should be addressed to Alfred Maroyi; [email protected]

    Received 5 September 2016; Revised 25 October 2016; Accepted 20 November 2016; Published 1 January 2017

    Academic Editor: Rainer W. Bussmann

    Copyright © 2017 Alfred Maroyi.This is an open access article distributed under theCreative CommonsAttribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Lippia javanica occurs naturally in central, eastern, and southern Africa and has also been recorded in the tropical Indiansubcontinent. The potential of L. javanica as herbal or recreational tea and herbal medicine and its associated phytochemistryand biological properties are reviewed. The extensive literature survey revealed that L. javanica is used as herbal tea and hasethnomedicinal applications such as in colds, cough, fever,malaria, wounds, diarrhoea, chest pains, bronchitis, and asthma.Multipleclasses of phytochemicals including volatile and nonvolatile secondary metabolites such as alkaloids, amino acids, flavonoids,iridoids, and triterpenes as well as several minerals have been identified from L. javanica. Scientific studies on L. javanicaindicate that it has a wide range of pharmacological activities which include anticancer, antiamoebic, antidiabetic, antimalarial,antimicrobial, antioxidant, antiplasmodial, and pesticidal effects. Although many of the traditional uses of L. javanica have beenvalidated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved.Lippia javanica is popular as both herbal and recreational tea, but there is need for more precise studies to evaluate the safety andclinical value of its main active crude and pure compounds and to clarify their mechanisms of action.

    1. Introduction

    Lippia javanica (Burm.f.) Spreng. (Verbenaceae) (Figure 1(a))has a long history of traditional uses in tropical Africaas indigenous herbal tea or tisane (Figure 1(b)), refresh-ing beverage, or food additive based on its perceivedhealth and medicinal properties. Lippia javanica is rich involatile oil, particularly caryophyllene, carvone, ipsenone,ipsdienone, limonene, linalool, myrcene, myrcenone, oci-menone, p-cymene, piperitenone, sabinene, and tagetenone[1–5]. Research by Viljoen et al. [3] revealed that the essentialoil profiles of L. javanica are characterized by inter- andintraspecies variations because they are produced by differentmetabolic pathways. Using cluster analysis, Viljoen et al. [3]identified five chemotypes of L. javanica in South Africaand Swaziland, myrcenone-rich type (36–62%), carvone-richtype (61–73%), piperitenone-rich type (32–48%), ipsdienone-rich type (42–61%), and linalool-rich type (>65%). The

    relative proportion of the chemical constituents of L. javanicaessential oil is important as this determines the biologicalproperties of the species chemotypes.

    Lippia javanica belongs to the Verbena or vervain family(Verbenaceae) comprising approximately 32 genera and 840species [97]. The genus Lippia L. is named after AugustinLippi (1678–1701), an Italian botanist and natural historianwho was killed in Ethiopia at the age of 23 [98]. Phylogeneticrelationships within family Verbenaceae demonstrated thatgenus Lippia and other closely related genera, namely,AloysiaPaláu, Lantana L., and Phyla Lour., are not monophyletic[97]. The boundaries separating these four genera are his-torically weak, with many taxonomic researchers includingspecies belonging toAloysia, Lantana, and Phyla in the genusLippia [99]. Lippia and Lantana genera are the most difficultto separate, as species of these two genera show similaritiesin their inflorescences that are spicate, often subcapitateduring anthesis and elongating in fruit and pedunculated

    HindawiEvidence-Based Complementary and Alternative MedicineVolume 2017, Article ID 6746071, 34 pageshttps://doi.org/10.1155/2017/6746071

    https://doi.org/10.1155/2017/6746071

  • 2 Evidence-Based Complementary and Alternative Medicine

    (a) (b)

    Figure 1: (a) Lippia javanica (Burm.f.) Spreng. flowers and leaves (photo: BT Wursten) and (b) L. javanica herbal tea traded as Zumbani inZimbabwe (http://specialityfoods.co.zw/product/zumbani/).

    [98]. According to de Campos et al. [100], the genus Lippiacomprises about 200 species of herbs, shrubs, and smalltrees distributed throughout south and central America andtropical Africa. Only 15 Lippia species have been recordedin tropical Africa [101]. The specific name “javanica” wasgiven by theDutch Botanist Nicolaas Laurens Burman (1734–1793) in 1768, whomistakenly thought that the type specimenwas collected in Java, Indonesia [102]. He placed the speciesin the genus Verbena, and the German botanist Sprengel(1766–1833) transferred Burman’s name to the genus Lippiain 1825 [103]. Lippia javanica is morphologically similar to L.scaberrima Sond. but is much taller and its bracts are shorterthan the flowers (Figure 1(a)), while L. scaberrima has manystems arising from ground level and is usually less than 0.5metres high, and its bracts are not longer than the flowers[104].

    Lippia javanica is an erect woody perennial herb orshrub of up to 4.5m tall, with strong aromatic leaves whichgive off a lemon-like fragrance when crushed [105]. Stemsare brownish, usually erect or spreading with short stifftubercle-based whitish hairs and small glands, and branchedwith inflorescences in nearly all axils. Leaves are oppositeor in whorls of 3, blades lanceolate to oblong and denselypubescent, rounded and then cuneate at the base, andcrenate-serrate or closely serrulate on themargins except nearthe leaf base [106]. Flowers occur in conical or oblong spikes,purple or dull-reddish in fruit, dark brownish on drying [101,106]. The flowers are sessile or with short peduncles, lowerbracts of spikes ovate and upper bracts smaller, pubescent,glandular, and densely spreading [101]. The calyx is 2-lobed,half as long as the corolla, pubescent, and densely spreading.The corolla is white, yellowish-white to greenish (Figure 1(a)),usually with a yellow throat, glandular and pubescent outsidein the upper half, tube narrowly funnel-shaped from a narrowbase [101, 106]. Anthers are sulphur-yellow and nutlets arebrown and half ovoid [101, 106].

    Lippia javanica occurs naturally in central, eastern, andsouthern Africa (Figure 2) and has also been recorded in thetropical Indian subcontinent [12, 13, 23, 39, 47, 61]. In sub-Saharan Africa, the species is native to Angola, Botswana,Central African Republic, Democratic Republic of Congo,Ethiopia, Kenya, Malawi, Mozambique, South Africa, Swazi-land, Tanzania, Uganda, Zambia, Zanzibar, and Zimbabwe.

    1000 km

    Figure 2: Lippia javanica naturally occurs in central, eastern, andsouthern Africa.

    Lippia javanica has been recorded in low to high altitude(0–2350m above sea level) woodlands and wooded grass-lands, scrub bushland, and grassy rocky kopjes, in riverinevegetation, and on margins of dambos and swampy ground,sometimes on termite mounds, in montane grasslands, andon evergreen forest margins, also in disturbed ground besideroads, forest clearings, plantations, and cultivated land andbecoming a weed in derived rangelands [101, 106].This showsthat the plant is highly adaptable to a wide range of climatic,soil, and vegetation conditions.

    2. Traditional Uses of Lippia javanica

    Lippia javanica is used for a wide variety of traditional uses(Table 1). Based on literature, the most important traditionalapplications include its uses as herbal tea and ethnomedicinalapplications for (in descending order of importance) colds,cough, fever or malaria, wounds, repelling mosquitos, diar-rhoea, chest pains, bronchitis, and asthma (Figure 3). Thesedifferent uses are discussed in the following seven sections:

    http://specialityfoods.co.zw/product/zumbani/

  • Evidence-Based Complementary and Alternative Medicine 3

    Table1:Tradition

    aluses

    ofLippiajavanica

    incentral,easte

    rn,and

    southern

    Africa.

    Use

    Plantp

    art(s

    )used

    Mod

    eofu

    seCou

    ntry

    practised

    Reference(s)

    Food

    uses

    Food

    additiv

    eLeaves,twigs

    Leaves

    andtwigsb

    oiledtogether

    with

    maize,cassava,groun

    dnuts,andcommon

    tea

    (Cam

    elliasin

    ensis

    (L.)Ku

    ntze)

    Kenya

    [6]

    Herbaltea

    Leaves

    Leaves

    canbe

    sundriedforlater

    use

    Botsw

    ana,South

    Africa,and

    Zimbabw

    e[7–11]

    Leafyvegetable

    Leaves

    Eatenas

    vegetablew

    ithmeato

    rfish

    India

    [12,13]

    Respira

    tory

    problem

    s

    Asthma

    Leaves,twigs

    Decoctio

    ntakenorallyor

    smokeinh

    aled

    SouthAfrica,

    Zimbabw

    e[14

    –17]

    Blockedno

    seLeaves

    Leafdecoctionof

    L.javanica

    alon

    etaken

    orallyor

    mixed

    with

    anyof

    theses

    pecies:

    Brachylaenaun

    ifloraHarv.,

    Clau

    sena

    anisa

    ta(W

    illd).H

    ook.f.ex

    Benth.,C

    lematis

    brachiataTh

    unb.,C

    ombretum

    molleR.

    Br.exG.D

    on,E

    ucalyptusgrand

    isW.H

    ill,

    Helichrysum

    krau

    ssiiSch.B

    ip.,Krau

    seolamosam

    bicin

    aPax&Hoff

    m.,Plectra

    nthu

    sneochilusS

    chltr.,Senecio

    serratuloidesD

    C.,orT

    richilia

    emetica

    Vahl

    takenorally

    SouthAfrica

    [18]

    Bron

    chitis

    Leaves,roo

    ts,andste

    ms

    Leafinfusio

    nof

    L.javanica

    alon

    etaken

    orallyor

    appliedto

    skin

    asointmento

    rleafand

    stem

    infusio

    nof

    L.javanica

    mixed

    with

    leaves

    ofAr

    temisiaafra

    Jacq.exWilld.taken

    orally

    Botsw

    ana,South

    Africa

    [15,19–22]

    Chestp

    ains

    Leaves,roo

    ts

    Leaves

    androotso

    fL.javanica

    alon

    echewe

    dor

    decoctiontakenorallyor

    used

    inwashes

    andpo

    ultic

    esor

    smokeinh

    aled

    or“im

    biza,”decoctionprepared

    from

    L.javanica

    and

    Cyrtanthus

    obliquu

    s(L.f.)

    Aito

    n,takenorallyor

    leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofanyof

    theses

    pecies:B

    rachylaena

    transvaalensis

    Hutch.exE.

    Phillips&

    Schw

    eick.,C.

    brachiata,E.

    grandis,H

    .kraussii,orT

    .emetica

    takenorallyor

    leafjuice

    takenorallywith

    cloveso

    fAllium

    sativ

    umL.

    Bang

    ladesh,

    Ethiop

    ia,and

    SouthAfrica

    [14,18,23–27]

    Colds

    Leaves,twigs

    Leafinfusio

    nof

    L.javanica

    alon

    etaken

    orallyor

    inhaledor

    appliedas

    anointmento

    r“im

    biza,”decoctionprepared

    from

    L.javanica

    andC.

    obliquu

    s,takenorally

    Botsw

    ana,Ke

    nya,

    SouthAfrica,and

    Zimbabw

    e

    [15,16,19,21,27–

    32]

    Cou

    ghLeaves,

    stems,and

    twigs

    Leaves

    ofL.javanica

    alon

    echewed

    orinfusio

    ninhaledor

    takenorallyor

    appliedas

    anointmento

    rleafand

    stem

    infusio

    nof

    L.javanica

    mixed

    with

    leaves

    ofanyof

    these

    species:Ac

    anthosperm

    umgla

    bratum

    (DC.)W

    ild.,A.

    afra,B

    .uniflora,B

    .transvaalensis,

    BrideliacatharticaBe

    rtol.,C.

    anisa

    ta,C

    .brachiata,C

    .molle,

    E.grandis,H.kraussii,K

    .mosam

    bicin

    a,P.neochilus,Psidium

    guajavaL.,S.serratuloides,Terminaliaseric

    eaBu

    rch.

    exDC.,Tetradeniarip

    aria(H

    ochst.)

    Cod

    d,or

    T.em

    etica

    takenorally

    Botsw

    ana,

    Ethiop

    ia,Sou

    thAfrica,and

    Zimbabw

    e

    [15,16,18–

    21,26,30,32]

    Influ

    enza

    Leaves,roo

    tsDecoctio

    ntakenorally

    Mozam

    biqu

    e,SouthAfrica

    [7,33–36]

    Lung

    infections

    Leaves

    Infusio

    nstakenorally

    SouthAfrica

    [37]

  • 4 Evidence-Based Complementary and Alternative Medicine

    Table1:Con

    tinued.

    Use

    Plantp

    art(s

    )used

    Mod

    eofu

    seCou

    ntry

    practised

    Reference(s)

    Measle

    sLeaves,stems

    Leafdecoctionof

    L.javanica

    alon

    etaken

    orallyor

    body

    washedwith

    infusio

    nor

    leafand

    stem

    infusio

    nof

    L.javanica

    mixed

    with

    leaves

    ofA.

    afra

    takenorally

    Kenya,South

    Africa,and

    Zimbabw

    e[14

    ,20,38]

    Pneumon

    iaLeaves

    Ointm

    entrub

    bedon

    chestand

    abdo

    men

    Zimbabw

    e[14

    ]Re

    spira

    tory

    disorders

    Leaves

    Decoctio

    ntakenorally

    India,SouthAfrica

    [39–

    41]

    Runn

    yno

    seLeaves,roo

    ts

    Leafandroot

    decoctionof

    L.javanica

    alon

    etaken

    orallyor

    leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofanyof

    theses

    pecies:B

    .transvaalensis,B

    .cathartica

    ,C.anisata,C

    .brachiata,E.

    grandis,Hypoxisspp.,K

    .mosam

    bicin

    a;P.guajava,S.serratuloides,P.

    neochilus,or

    T.em

    etica

    takenorally

    SouthAfrica

    [18]

    Shortnesso

    fbreath(dyspn

    oea)

    Leaves

    Decoctio

    ntakenorallyor

    body

    washedwith

    decoction

    Zimbabw

    e[14

    ]

    Sore

    throat

    Leaves

    Leafdecoctionof

    L.javanica

    alon

    etaken

    orallyor

    leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofE.

    grandiso

    rT.ripariatakenorally

    SouthAfrica

    [18]

    Tonsillitis

    Leaves

    Leafdecoctionof

    L.javanica

    alon

    etaken

    orallyor

    leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofE.

    grandistaken

    orally

    SouthAfrica

    [18]

    Tuberculosis

    Leaves

    Leafdecoctionof

    L.javanica

    alon

    etaken

    orallyor

    “imbiza,”decoctionprepared

    from

    L.javanica

    andC.

    obliquu

    s,takenorally

    SouthAfrica,

    Ugand

    a[24,42,43]

    Gastro

    intestina

    ldise

    ases

    Amoebiasis

    Leaves,twigs

    Decoctio

    ntakenorally

    Kenya

    [6]

    Anthelm

    intic

    sLeaf

    Infusio

    nstakenorally

    SouthAfrica

    [40]

    Diarrho

    eaLeaves,roo

    tsDecoctio

    ntakenorally

    Kenya,

    Mozam

    biqu

    e,SouthAfrica

    [17,29,34,37,44]

    Gangrenou

    srectitis

    Leaves

    Infusio

    nstakenorally

    SouthAfrica

    [45]

    Prop

    hylacticagainstd

    iarrho

    eaLeaves

    Infusio

    ntakenorally

    SouthAfrica

    [40]

    Vomiting

    Leaves

    Decoctio

    ntakenorally

    Zanzibar,Tanzania

    [46]

    Fever,malaria,and

    asinsectrepellent

    Fever

    Leaves,

    stems,and

    twigs

    Leafandtwigdecoctionof

    L.javanica

    alon

    etaken

    orallyor

    leafandste

    minfusio

    nof

    L.javanica

    mixed

    with

    leaves

    ofanyof

    theses

    pecies:A

    .afra

    ,B.transvaalensis,C

    .anisata,C

    .molle,

    E.grandis,P.gua

    java,S.serratuloides,T.riparia,orT

    .emetica

    takenorally

    SouthAfrica,

    Zimbabw

    e[14

    ,16,18,20]

    Gettin

    grid

    oflice,insects,andlicea

    ndas

    mosqu

    itorepellent

    Leaves,twigs,

    andwho

    leplant

    Usedin

    washesa

    ndpo

    ultic

    esor

    asste

    amor

    sprayedor

    burnttochasea

    way

    mosqu

    itoes

    Ethiop

    ia,Sou

    thAfrica,and

    Zimbabw

    e[4,26,34,47–51]

    Malaria

    Leaves,roo

    tsDecoctio

    ntakenorally

    Mozam

    biqu

    e,SouthAfrica

    [17,33,52]

    Prop

    hylacticagainstm

    alaria

    Leaves

    Infusio

    ntakenorally

    SouthAfrica

    [40]

  • Evidence-Based Complementary and Alternative Medicine 5

    Table1:Con

    tinued.

    Use

    Plantp

    art(s

    )used

    Mod

    eofu

    seCou

    ntry

    practised

    Reference(s)

    Wound

    s,injurie

    s,pain,and

    skin

    infec

    tions

    Abdo

    minalpains

    Leaves

    Leaves

    chew

    edandjuices

    wallowed

    Zimbabw

    e[14

    ]Ac

    neLeaves

    Not

    specified

    Botsw

    ana

    [22]

    Antidotes

    Roots

    Usedas

    antid

    otefor

    food

    poiso

    ning

    Botsw

    ana

    [22]

    Backache

    Roots

    Infusio

    ntakenorally

    SouthAfrica,

    Zimbabw

    e[14

    ,20]

    Bleeding

    from

    then

    ose(epistaxis)

    Leaves

    Freshleaves

    inserted

    into

    nose

    orpo

    wderedleaves

    sniffed

    SouthAfrica,

    Zimbabw

    e[14

    ,53]

    Boils

    Leaves

    Infusio

    ntakenorally

    SouthAfrica

    [54]

    Chickenpo

    xLeaves

    Usedin

    washesa

    ndpo

    ultices

    oras

    steam

    SouthAfrica

    [50]

    Earache

    Leaves

    Decoctio

    ntakenorallymixed

    with

    leaves

    ofE.

    grandis

    SouthAfrica

    [18]

    Febrile

    rashes

    Leaves

    Infusio

    nstakenorally

    SouthAfrica

    [40]

    Headache,migraine

    Leaves,roo

    tsLeafandroot

    decoctionof

    L.javanica

    alon

    etaken

    orallyor

    leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofanyof

    theses

    pecies:B

    .cathartica

    ,C.brachiata,E

    .grand

    is,T.rip

    aria,

    andT.em

    etica

    takenorally

    Kenya,South

    Africa,and

    Zimbabw

    e[14

    ,18,33,34,38]

    Inflammation

    Leaves

    Not

    specified

    SouthAfrica

    [41]

    Pubics

    ores

    Leaves

    Decoctio

    ntakenorallymixed

    with

    leaves

    ofAc

    anthosperm

    umau

    strale(Lo

    efl.)Ku

    ntze

    Swaziland

    [55]

    Scabies

    Leaves,roo

    tsInfusio

    ntakenorallyor

    used

    inwashesa

    ndpo

    ultic

    esor

    asste

    amSouthAfrica,

    Zimbabw

    e[14

    ,50,54]

    Shingles

    Leaves,twigs,

    androots

    Appliedas

    anointment

    SouthAfrica

    [15]

    Skin

    disorders,such

    asheatrash

    scratches,sting

    s,andbites

    Leaves,twigs

    Appliedas

    anointmento

    r“im

    biza,”decoctionprepared

    from

    L.javanica

    andC.

    obliquu

    s,takenorally

    SouthAfrica

    [21,27]

    Sores

    Leaves

    Decoctio

    nof

    L.javanica

    mixed

    with

    bark

    ofAc

    aciaburkeiBe

    nth.,O

    zoroaengle

    riR.

    Fern.

    &A.Fern.,Scle

    rocaryabirrea

    (A.R

    ich.)H

    ochst.,Syzygium

    cordatum

    Hochst.ex

    Krauss,

    andTabernaemontana

    elegans

    Stapftaken

    orally

    SouthAfrica

    [56]

    Sore

    eyes,cataracts

    Leaves,roo

    tsJuices

    queezedinto

    eyes

    Botsw

    ana,

    Zimbabw

    e[14

    ,22]

    Sprained

    joints

    Roots

    Root

    powdera

    ppliedto

    scarificatio

    nsarou

    ndsprained

    joints

    SouthAfrica

    [20]

    Ulcers

    Leaves

    Juicetaken

    orallywith

    cloveso

    fA.sativum

    Bang

    ladesh

    [23]

    Wou

    nds

    Leaves

    Freshleaves

    wrapp

    edarou

    ndwou

    ndto

    enhanceh

    ealin

    gor

    infusio

    ntakenorally

    Kenya,South

    Africa

    [54,57]

    Ethn

    oveterinaryu

    ses

    Disinfectin

    gsuspectedanthrax-infeste

    dmeat

    Who

    leplant

    Who

    leplantsused

    todisin

    fectsuspectedanthrax-infeste

    dmeat

    SouthAfrica

    [20]

    Gettin

    grid

    ofticks

    andother

    ectoparasites

    Leaves,twigs,

    andwho

    leplant

    Crushedleaves

    mixed

    with

    water

    andsprayed,twigsu

    sedas

    bedd

    ingin

    fowlrun

    sSouthAfrica,

    Zimbabw

    e[58–60]

    Lice

    repellant

    Who

    leplant

    Who

    leplantu

    sedto

    repelliceinpo

    ultry

    India

    [61]

    Milk

    preservativ

    eStem

    Stem

    appliedto

    milk

    gourdbefore

    milk

    ferm

    entatio

    nKe

    nya

    [62]

  • 6 Evidence-Based Complementary and Alternative Medicine

    Table1:Con

    tinued.

    Use

    Plantp

    art(s

    )used

    Mod

    eofu

    seCou

    ntry

    practised

    Reference(s)

    Otheruses

    Anaem

    iain

    pregnancy

    Leaves

    Decoctio

    ntakenorally

    Zanzibar,Tanzania

    [46]

    Broo

    mWho

    leplant

    Who

    leplantscutand

    tiedtogether

    tomaker

    ough

    broo

    ms

    SouthAfrica

    [53]

    Cancer

    Leaves

    “Imbiza,”decoctionprepared

    from

    L.javanica

    andC.

    obliquu

    s,takenorally

    SouthAfrica

    [27]

    Cerem

    onial

    Leaves,w

    hole

    plant

    Usedbefore

    andaft

    erfuneralsor

    placed

    onpatie

    nts’bedaft

    ercircum

    cisio

    nKe

    nya,South

    Africa

    [31,58,63]

    Con

    vulsion

    sLeaves

    Leaves

    rubb

    edon

    face

    Zimbabw

    e[14

    ,64]

    Diabetes

    Leaves

    “Imbiza,”decoctionprepared

    from

    L.javanica

    andC.

    obliquu

    s,takenorally

    SouthAfrica

    [27]

    Fatig

    ueor

    tiredness

    Leaves

    Leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofA.

    glabratum

    orE.

    grandiso

    rT.riparia

    takenorally

    SouthAfrica

    [18]

    Fence

    Who

    leplant

    Plantedarou

    ndho

    mesteads

    Ethiop

    ia[26]

    Fodd

    erLeaves

    Leaves

    eatenby

    goats

    Kenya

    [31]

    Fuelw

    ood

    Who

    leplant

    Who

    leplantu

    sedas

    fuelw

    ood

    Zanzibar,Tanzania

    [46]

    Hum

    anim

    mun

    odeficiency

    virus(HIV

    )or

    acqu

    iredim

    mun

    odeficiency

    synd

    rome

    (AID

    S)symptom

    sLeaves

    “Imbiza,”decoctionprepared

    from

    L.javanica

    andC.

    obliquu

    swhich

    istakenorally

    SouthAfrica

    [65,66

    ]

    Kidn

    eyprob

    lems

    Root

    50groot

    powd

    erbo

    iledin

    2litreso

    fwater;patient

    takesa

    cupof

    thismixture

    once

    per

    dayfor3

    days

    Swaziland

    [67]

    Madness

    Leaves,w

    hole

    plant

    Body

    washedwith

    leafinfusio

    nMalaw

    i,Zimbabw

    e[14

    ,68]

    Marasmicinfants

    Roots

    Infusio

    nsused

    tobath

    infants

    SouthAfrica,

    Zimbabw

    e[14

    ,20]

    Night

    blindn

    ess

    Leaves

    Face

    washedwith

    infusio

    nZimbabw

    e[14

    ]Nightmares

    Not

    specified

    Not

    specified

    Zimbabw

    e[64]

    Pre-,intra-,andpo

    stpartum

    complications

    Stem

    ,roo

    tsSm

    earp

    owdero

    froo

    torstem

    Kenya

    [69]

    Preventin

    god

    oursor

    beingused

    indo

    ors

    tofre

    shen

    air

    Leaves,w

    hole

    plant

    Leaves

    sprin

    kled

    intoiletsto

    prevento

    dourso

    rwho

    leplantp

    lacedin

    vase

    orroom

    Kenya,South

    Africa

    [31,35,58]

    Protectio

    nagainstd

    ogsa

    ndcrocod

    iles

    Leaves

    Leaves

    smearedon

    body

    SouthAfrica

    [70]

    Psycho

    tropicb

    ehaviour

    Leaves

    Infusio

    ntakenorally

    Swaziland

    [71]

    Removingbadluck

    Leaves

    Face

    andhand

    swashedwith

    infusio

    nof

    L.javanica

    leaves

    mixed

    with

    C.molleleaves

    Swaziland

    [72]

    Sleeplessn

    ights

    Leaves

    Leafdecoctionof

    L.javanica

    mixed

    with

    leaves

    ofE.

    grandisand

    T.rip

    ariatakenorally

    SouthAfrica

    [18]

    Todrivea

    way

    badspirits

    Leaves

    Body

    washedwith

    infusio

    nZimbabw

    e[14

    ]To

    preventinfantsfro

    mcontracting

    illnesscaused

    byfather

    ormother

    committingadultery

    Leaves

    Leaves

    rubb

    edon

    forehead,elbow

    s,andkn

    eesa

    fterc

    ommittingadultery

    Zimbabw

    e[14

    ]

    Venerealdiseases

    Roots

    Decoctio

    ntakenorally

    Mozam

    biqu

    e[44]

    Weakjoints

    Leaves

    Decoctio

    ntakenorally

    Zimbabw

    e[14

    ]

  • Evidence-Based Complementary and Alternative Medicine 7

    0 2 4 6 8 10 12 14 16

    Asthma

    Bronchitis

    Chest pains

    Diarrhoea

    Mosquito repellent

    Wounds

    Fever/malaria

    Herbal tea

    Cough

    Colds

    Times found in literature

    Figure 3: Main ethnobotanical applications of Lippia javanica in central, eastern, and southern Africa. An ethnobotanical use is countedonly once per publication.

    Food Uses; Respiratory Problems; Gastrointestinal Diseases;Fever, Malaria, and Insect Repellent; Wounds, Injuries, Pain,and Skin Infections; Ethnoveterinary Uses; and Other Uses.

    2.1. Food Uses. Leaves and twigs of Lippia javanica are usedas food additives in Kenya [6] and leafy vegetable in India[12, 13]. Lippia javanica is popular as herbal tea, particularlyin Botswana, South Africa, and Zimbabwe [7–11]. Lippiajavanica herbal tea is prepared by steeping fresh or driedleaves, stems, or twigs in boiling water and letting them standfor two to five minutes to release flavour, with or withoutmilk and sugar added according to taste. A stronger brew,known as a decoction, is prepared by boiling fresh or driedleaves, stems, or twigs for more than five minutes. The herbaltea prepared from L. javanica leaves, stems, or twigs has alemon or vanilla aroma and is often used as a common tea(i.e., C. sinensis) substitute or a few leaves, stems, or twigsare added to C. sinensis to provide a lemon or vanilla aroma.According to Sõukand and Kalle [87], herbal tea or tisaneis an English term used to denote a decoction or infusionmade of herbs for medicinal purposes. When L. javanica isused as medicinal herbal tea, it is consumed for a limitednumber of days to treat a specific condition like asthma inZimbabwe [14], bronchitis in South Africa [19], chest painsin Zimbabwe and South Africa [14, 24], colds in Kenya,South Africa, and Zimbabwe [19, 20, 28–30], cough in SouthAfrica and Zimbabwe [19, 20, 30, 53], and other diseases(see Table 1). From literature, it seems L. javanica herbaltea evolved over the years from medicinal tea decoctionsor infusions to nonmedicinal uses, where the herbal teais now drunk for recreation and enjoyment. According toShikanga et al. [7], L. javanica tea is appreciated throughoutits distributional range as a general health tonic and alsobecause it is naturally caffeine-free and has a calming andrelaxing effect. Research done by other workers, for example,Manenzhe et al. [2], Shikanga et al. [7], Parrant [8], Olivieret al. [81], Motlhanka and Makhabu [9], and Bhebhe et al.[10, 11], revealed that L. javanica is a popular recreational teain southern Africa, consumed on a daily basis within a food

    context, while medicinal infusions or tisanes of L. javanicaare taken for a specific medical purpose. During the past20 years, the use of herbal teas has increased globally [107]because of their functional properties and consumer interestin the health promoting properties of such beverages [108].The other advantage associated with L. javanica usage is thatthe leaves can be sun-dried and later boiled in water anddrunk as herbal tea [9].

    Most of L. javanica used as herbal tea in rural andperiurban communities in central, eastern, and southernAfrica is still collected from the wild, although small-scale cultivation has become necessary as it is marketed asherbal tea in Botswana under the brand name “Mosukudu”or “Mosukujane” [109] and in Zimbabwe as “Zumbani”(Figure 1(b)). Although considerable quantities of L. javanicaare sold in local markets in Botswana and Zimbabwe andalso traded on the Internet, there is no data on presentproduction levels, traded volumes, values, and export figuresin these two countries. Research by Whiteside [110] showedthat sales of L. javanica tea bags generated an income ofR20300.00 (US$5718) during 1994/1995 in Botswana. Thereis increased demand for L. javanica herbal tea especiallyin the light of growing health consciousness worldwide,with the estimated potential demand for the species and itsproducts around 100 tonnes per year on the local marketand 1000 tonnes per year on the export market (http://bio-innovation.org/work/fever-tea-tree/). Considering the rapidgrowth of the herbal tea industry worldwide and the increas-ing demand for L. javanica products, there is need for theimprovement of L. javanica products as well as developmentof new products. Therefore, L. javanica has potential to makethe transition from limited local use to commercial andinternational product. Lippia javanica has been identifiedas one of the few plant species that should be integratedin the domestication process in farming systems in sub-Saharan Africa to supportmedicinal, nutritional, and incomesecurity of local communities [107, 111]. According to VanWyk [111], L. javanica is of commercial value as herbal tea andhealth drinks. Therefore, commercialization of L. javanica is

  • 8 Evidence-Based Complementary and Alternative Medicine

    unlikely to be viable if the product is sorely harvested fromthe wild. In the same line commercialization of L. javanicamight be more worthy if other products other than tea arederived from the plant.

    2.2. Respiratory Problems. The different parts of L. javanica,for example, the leaves and twigs, are used for the treatmentof asthma, coughs, colds, influenza, pneumonia, tuberculosis,and bronchial problems in Bangladesh, Botswana, Ethiopia,Kenya, South Africa, and Zimbabwe [14–16, 19, 20, 23, 25, 26,28–32, 53, 112]. In Bangladesh, leaf infusion of L. javanica istaken orally mixed with 3-4 pieces of cloves ofA. sativum, 2-3times daily as remedy for chest pains [23]. In Ethiopia, leavesof L. javanica are chewed with butter as remedy for chestpains and cough [26]. In India, L. javanica leaf decoctionis taken orally as remedy for respiratory disorders [39]. InKenya, leaves are sniffed [31] or half glass of hot leaf infusionis taken orally three times a day [28, 29] as remedy for coldsand cough. Research done by Davids et al. [19] in SouthAfrica revealed that about 50 g of leaves is added to a cupof boiling water to produce an infusion which is taken orallyas remedy for coughs, colds, and bronchial problems or theinfusion is applied to the skin or mixed with Vaseline tomake an ointment. In South Africa, leaf or twig decoctionis taken orally for asthma, colds, and cough [16, 53], leavesare used in washes and poultices for chest pains [25], andleaves are boiled for 5 minutes and one cup of extract is takenorally thrice a day for chest pains and tuberculosis [24, 42].According to York [18], two handfuls of L. javanica leaves areboiled in two litres of water and patient is steamed once ortwice a day to treat coughs, chest pain, headaches, fever, chills,a sore throat, or a blocked nose. This decoction can also betaken orally by drinking half a cup daily [18]. Alternatively,a handful of L. javanica roots or leaves are mixed with ahandful leaves of A. glabratum or B. transvaalensis or B.uniflora or B. cathartica or C. anisata or C. brachiata orC. molle or E. grandis or H. kraussii or Hypoxis spp. or K.mosambicina or P. neochilus or P. guajava or S. serratuloides orT. sericea or T. riparia or T. emetica to treat blocked nose,chest pain, cough, earache, fatigue, fever, influenza, headache,runny nose, sleepless nights, sore throat, tiredness, andtonsillitis [18]. Leaf and stem infusion of L. javanica are takenorally together with A. afra by the Zulu people in SouthAfrica as remedy for bronchial ailments, colds, and cough[20]. “Imbiza,” a popular herbal decoction prepared from L.javanica and C. obliquus, is used by the Zulu people in SouthAfrica as herbal tonic and an immune booster and also forthe treatment of cancer, chest pains, colds, diabetes, HIV orAIDS symptoms, skin infections, and tuberculosis [27]. Insome communities in South Africa, L. javanica leaf or rootinfusion is taken orally as remedy for influenza and malaria[33] and respiratory disorders [40, 41]. In Zimbabwe, leafor root decoction is taken orally or smoke of burnt leavesand roots is inhaled as remedy for chest pains [14] and leafand twigs are boiled in water and infusion is taken orally asremedy for colds and cough [30]. According to Gelfand etal. [14], Shona people in Zimbabwe rub leaf ointment of L.javanica on the chest and abdomen as remedy for pneumoniaand leaf decoction is taken orally and body washed with leaf

    decoction as remedy for shortness of breath or dyspnoea. InSouth Africa, a leaf and stem infusion of L. javanica are takenorally together with leaves of A. afra as remedy for measles[20].

    Based on literature, inhalation of smoke from L. javanicaappears to be a popular remedy for asthma, chest pains,colds, and chronic coughs in Botswana, South Africa, andZimbabwe [14, 15, 20, 32]. In Botswana, L. javanica leafinfusion vapour is inhaled as remedy for colds and cough[32]. In SouthAfrica, for example, leaves and twigs are burnedand smoke is inhaled as remedy for asthma and cough [15]or steam from leaf infusions is inhaled or hot leaf infusionsare taken orally against colds and cough [20]. In Zimbabwe,smoke of burnt leaves and roots is inhaled as remedy for chestpains [14].

    2.3. Gastrointestinal Diseases. The leaf and root decoction orinfusions of L. javanica are used as remedies of the digestivesystem diseases such as cholera, diarrhoea, and dysentery.For example, in Mozambique, root decoction is taken orallyas remedy for a type of diarrhoea commonly known as“chinhamucaca” which is characterized by milky diarrhoeaaccompanied by vomiting in children [44]. Leaf decoctionis used as herbal medicine for diarrhoea in Kenya [113]. InSouth Africa, the leaves of L. javanica are crushed and mixedwith cold or hot water and the mixture is then sieved and aquarter of a cup (75mL) is taken twice a day until diarrhoeasubsides [34]. The Venda people in South Africa use leafinfusions as prophylactic against diarrhoea [40]. Researchdone by Palgrave et al. [37] in South Africa revealed that teainfusions of the L. javanica leaves are used as remedies forHIV/AIDS opportunistic infections such as lung infectionsand diarrhoea. Previous research inMozambique [114], SouthAfrica [115], and Zimbabwe [116] showed that gastrointestinaldisorders, particularly cholera, diarrhoea, and dysentery areamong human diseases often treated with herbal medicines.For those patients diagnosed as having intestinal worms inVenda, South Africa, a leaf infusion of L. javanica leavesis used as an anthelmintic [40]. Therefore, these findingsillustrate that herbal medicines including L. javanica can playan important role in basic health care of local communitiesthrough treatment and management of cholera, diarrhoea,and dysentery.

    2.4. Fever, Malaria, and Insect Repellent. Traditionally, L.javanica is commonly used to treat fever and malaria andrepel insects throughout its distributional range [4, 14, 16,17, 33–35, 40, 48–50, 58–60]. In South Africa, a decoctionof fresh or air dried leaves is used to wash or steam bodyparts infested with lice [50]. In India, the whole plant is usedto repel lice in poultry [61]. In South Africa and Zimbabwe,whole plant or leaves are burnt to repel mosquitoes [4, 34,35, 48, 49, 58]. In South Africa and Zimbabwe, L. javanicais widely used to get rid of ticks and other ectoparasites; forexample, ticks are sprayed with crushed leaves mixed withwater or twigs are used as bedding in fowl runs [58–60].Leaf and twig decoction of L. javanica are taken orally asremedy for fever [16]. The Venda people in South Africa useleaf infusions of L. javanica as prophylactic against malaria

  • Evidence-Based Complementary and Alternative Medicine 9

    [40]. In Zimbabwe, leaf decoction is taken orally as remedyfor fever [14].

    Lippia javanica is also cultivated on a commercial scale bya rural community in Giyani, the Limpopo province, SouthAfrica, for the production of mosquito-repellent candles[117]. Clinical studies using human volunteers showed thatL. javanica repels no less than 95% of mosquitos, whereasmost mosquito repellents repel only 42% of them [118].Based on these findings, the Council for Scientific andIndustrial Research (CSIR), South Africa, signed a benefitsharing agreement with traditional healers allowing for thecommercial cultivation of L. javanica aimed at establishingan indigenous oil industry for rural development and large-scale production of antimosquito candles and other insectrepellents. The mosquito repellent is registered as a patentunder the Fertilisers, Farm Feeds and Stock Remedies Act(Act 36 of 1947) as a pest repellent [119]. These findings andthe establishment of a large-scale production of antimosquitocandles and other insect repellents strengthen the view thatL. javanica is a potential source of antipesticidal agentsand to some extent validate the traditional use of the plantspecies for insect pest control. Pesticidal plants such as L.javanica are increasingly being used as alternatives wheresynthetic products are unaffordable or are not available or areineffective. A number of studies have indicated that the use ofL. javanica as a pesticide is a long-standing tradition passeddown from generation to generation [120].

    2.5. Wounds, Injuries, Pain, and Skin Infections. Lippia javan-ica is used as remedy for a variety of skin infections andinjuries in Kenya, South Africa, Swaziland, and Zimbabwe.In SouthAfrica, leaf infusions are used to treat skin disorders,such as boils, chicken pox, febrile rashes, heat rashes,measles,scabies, scratches, and stings [20, 21, 40, 50, 54]. In Kenya,about 50 g of fresh leaves is wrapped around a fresh woundto enhance healing [57] and, in South Africa, leaf infusionsare taken orally as remedy for wounds [54]. In SouthAfrica, powder from burnt roots of L. javanica is appliedto scarifications made around sprained joints to facilitatehealing [20]. In Kenya and Zimbabwe, leaf infusion is takenorally to treatmeasles or a patient is washedwith leaf infusion[14, 38]. The Zulu people in South Africa take a mixtureof chopped handful leaves of L. javanica with the sameamount of bark of A. burkei,O. engleri, S. birrea, S. cordatum,and T. elegans boiled in two litres of water as an enemafor the treatment of sores [56]. In Swaziland, about 30 g ofL. javanica leaves and similar amount of Acanthospermumaustrale Kuntze are boiled in 5 litres of water and decoctionis taken as remedy for sores [55]. In Zimbabwe, root ashesof L. javanica mixed with fat are applied to the skin ofa patient with scabies [14]. Wound healing is a processwhich involves distinct overlapping phases of coagulation,inflammation, proliferation, and tissue remodelling [121].The same authors argued that a set of complex biochemicalevents takes place in a closely orchestrated cascade to repairthe wound and any errors in the wound healing processcan lead to delayed healing or formation of hypertrophicscars. Abubakar [122] argued that colonization of woundsby opportunistic microorganisms usually delays the wound

    healing process and/or may lead to infectious condition.Therefore, application of L. javanica on wounds and skininfections leads to disinfection, debridement, and provisionof a suitable environment for aiding the wound healingprocess. Lippia javanica has potential for therapeutic use inwound and skin diseases management, but there is needfor research on the safety, phytochemistry, and biologicalproperties of the species.

    2.6. EthnoveterinaryUses. The leaves, stems, twigs, andwholeplants of L. javanica are used as ethnoveterinary medicinein India, Kenya, South Africa, and Zimbabwe. The Xhosapeople in the Eastern Cape province, South Africa, use L.javanica leaves for the disinfection of meat that has beeninfected with anthrax [20]. In Kenya, the stem of L. javanicais used to preserve milk by applying it to the gourd beforemilk fermentation [62]. In India, whole plants are used aslice repellants while, in South Africa and Zimbabwe, crushedleaves mixed with water are used to get rid of ticks and twigsare used as bedding in fowl runs to get rid of ectoparasites[58–60].

    2.7. Other Uses. Lippia javanica is used as a good luck charm,to treat persons experiencing bad dreams, to ward off evilspirits, to protect one from lightening, and to protect thehome (Table 1). In Zimbabwe, L. javanica leaves are preparedas an infusion to treat persons experiencing nightmares [64].In both South Africa and Zimbabwe, evil spirits are cleansedby washing the body of an affected person by leaf infusion ofL. javanica [14, 123]. In Swaziland, 50 g leaves of L. javanicaand C. molle are ground into a powder and 5 litres of wateris added and face and hands are washed to remove badluck when exposed to a corpse [71]. In South Africa, thewhole plant is placed on a patient’s bed after the circumcisionceremony [58], to prevent odours and freshen surroundingair. A mixture of L. javanica leaves and roots is used toclean tools and hands before and after funerals, the stemsand leaves are used as brooms to sweep grave sites, and theentire plant is also used when coming from the mortuaryto remove bad spirits [58, 124]. The corpse is washed withL. javanica infusion after death to prevent odours formingor if the corpse has an odour, women place pieces of L.javanica in the nostrils of the corpse and sweep the roomwith twigs where the person was sleeping [58]. In KwaZuluNatal, South Africa, if the meat started to smell it will beboiled with L. javanica leaves to take away the smell [58].TheXhosa people in the Eastern Cape province, South Africa, useL. javanica leaves for the disinfection of meat that has beeninfected with anthrax [20]. In KwaZulu Natal, South Africa,leaves are sprinkled in toilets to prevent odours [58]. Leavesof L. javanica are sprinkled in houses for pleasant smell inthe Limpopo province, South Africa [35], and Kenya [31]. InKwaZulu Natal, South Africa, it is believed that a person canrepel snakes by placing a small stem with leaves on his orher head [58]. In Malawi, Swaziland, and Zimbabwe, peopleshowing sign of mental disorder, madness, or hystericaloutbursts are required towash their bodies with leaf infusions[14, 67, 68, 71].

  • 10 Evidence-Based Complementary and Alternative Medicine

    Table 2: Nutritional composition of Lippia javanica leaves.

    Caloric and nutritional composition Values ReferenceAsh 1.60 ± 0.001 g [13]Calorific value 50.64 ± 5.63 kcal [13]Crude fat 0.16 ± 0.001 g [13]Crude fibre 2.63 ± 0.002 g [13]Crude protein 1.22 ± 0.0004 g [13]Dry matter 15.46 ± 1.40 g [13]Moisture 90.44 ± 0.26 g [13]Total carbohydrate 6.55 ± 0.26 g [13]Vitamin C 22.42 ± 0.001mg [13]Ca 2856–9225 𝜇g g−1 [27]Mg 1598–5619 𝜇g g−1 [27]Fe 75–750 𝜇g g−1 [27]Mn 40.1 ± 1.16 𝜇g g−1 [27]Zn 15.6–27.3 𝜇g g−1 [27]Cu 3.0–8.5 𝜇g g−1 [27]Cr 0–2.7 𝜇g g−1 [27]Se 2.57 ± 0.19 𝜇g g−1 [27]Pb 0.38–1.19 𝜇g g−1 [27]Cd 0.53 ± 0.05 𝜇g g−1 [27]Co 0.19 ± 0.01 𝜇g g−1 [27]

    3. Phytochemical Constituents and NutritionalComposition of Lippia javanica

    Multiple classes of phytochemicals including volatile andnonvolatile secondary metabolites, such as alkaloids, aminoacids, flavonoids, iridoids, and triterpenes as well as severalminerals, have been identified from L. javanica [1–5, 7, 13, 27,73, 78, 81, 83–86, 88–94, 120, 123, 125–127]. Leaves, flowers,and twigs of L. javanica have a wide variety of the so-calledclassic nutrients, such as minerals, carbohydrates, proteins,fats, and vitamins (Table 2). Lippia javanica leaves are a goodsource of minerals such as cadmium, calcium, chromium,cobalt, copper, iron, magnesium, manganese, selenium, andzinc [27]. These authors assessed the levels of the elementsin L. javanica leaves and found the elements to be in thedecreasing order of Ca > Mg > Fe > Zn > Mn > Cu > Se >Cr > Pb > Co > Cd for total concentrations and Ca > Mg> Fe > Zn > Cu > Cr > Pb for water extractable forms. Theseresults corroborate an observation made by Sedaghathooret al. [128] that Ca and Mg are among the most abundantelements in tea plants. These mineral elements are importantin human nutrition since L. javanica is used as herbaltea and food additive (Table 1). Calcium, magnesium, iron,manganese, and zinc play a major role in activating someenzymes and regulating many responses of cells to stimuli[129]. Some of the mineral elements identified from L.javanica leaves are required by the human body for repair ofworn out cell tissues and strong bones and teeth and buildingof red blood cells and other related tissues.Therefore, since L.javanica has appreciable concentrations of mineral elementssuch as calcium, magnesium, iron, manganese, and zinc

    (Table 2) which are essential for enzyme metabolism, thesemineral elements could enhance the nutritional and curativeproperties of the species.

    Bhebhe et al. [10] determined the total phenolic and tan-nin content and radical scavenging activities of L. javanica,comparing it with Aspalathus linearis (Burm.f.) R. Dahlgren(Rooibos�), a commercial South African herbal tea, andother popular herbal teas in Zimbabwe (Table 3). Adansoniadigitata L., Fadogia ancylantha Schweinf., Ficus sycomorus L.,and Myrothamnus flabellifolius Welw. are indigenous herbalteas consumed in Zimbabwe. The tannin content of L.javanica is very low when compared to A. linearis (Rooibos)(Table 3). Lippia javanica has higher radical scavenging activ-ity than A. linearis (Table 3) which is probably due to highertotal phenolic content in comparison to A. linearis which is apopular herbal tea consumed by 10% of the global herbal teamarket [10]. In another study, Bhebhe et al. [11] determinedand compared the effect of several solvents, namely, hotwater, 50% methanol, ethanol, 50% ethanol, acetone, 50%acetone, and ethyl acetate, on phenolic composition and freeradical scavenging activity in common black tea, C. sinensis,and five other well-known herbal teas including L. javanica.In all the seven solvents used, L. javanica had higher totalphenolic content than C. sinensis implying that L. javanicais competitive to the black tea in terms of phenolic content.Shikanga et al. [7] found leaf extracts of L. javanica to havehigher phenolic content of 14.8 mg/g gallic acid equivalentof dry weight than flowers (9.9mg/g) and twigs (8.3mg/g).Phenolic compounds found in plants are known to play animportant role as antioxidants in exhibiting the medicinalproperties such as antibiotic, anti-inflammatory, anticancer,and antiallergic properties [10, 66, 130, 131].

    The compounds isolated from L. javanica are docu-mented and listed in Appendix A and their structures arepresented in Appendix B. Simple phenolic compounds andcaffeic acid and its derivatives are some of the compoundsthat have been identified in L. javanica and examplesinclude coumarin 1, 3,4-dihydroxy-𝛽-phenylethoxy-O-[4-𝛽-caffeoyl-𝛼-rhamnopyranosyl-(1,3)-O-𝛽-glucopyrano-side], commonly referred to as verbascoside 2, and 3,4-dihydroxy-𝛽-phenylethoxy-O-[6-𝛽-caffeoyl-𝛼-rhamnopy-ranosyl-(1,3)-O-𝛽-glucopyranoside] commonly referredto as isoverbascoside 3 isolated by Olivier et al. [81] from theaerial parts of the species. Nonvolatile diterpenes, known asiridoid-glycosides, have also been isolated from L. javanicaby Rimpler and Sauerbier [82] represented by theveside-Na4 and theveridoside 5. Mujovo et al. [83] isolated a longchain alkane “4-ethylnonacosane” 6 and four flavanonesapigenin 7, cirsimaritin 8, 6-methoxyluteolin 4-methylether 9, and 6-methoxyluteolin 3,4,7-trimethyl ether 10from ethanolic extracts of L. javanica leaves. Madzimureet al. [120] identified an array of phenolic glycosides andflavonoids which include crassifolioside 11, luteolin 12,diosmetin 13, chrysoeriol 14, tricin 15, isothymusin 16,eupatorin 17, 5-dimethyl noboletin 18, genkwanin 19,salvigenin 20, and an alkaloid xanthine 22. Ludere et al.[84] isolated lippialactone 21 from the ethyl acetate extractof aerial parts of L. javanica. Neidlein and Staehle [85] andDlamini [86] isolated 19 amino acids, compounds 23 to

  • Evidence-Based Complementary and Alternative Medicine 11

    Table 3: Total phenolic content (TPC) as gallic acid equivalents (GAE) and tannin content as leucocyanidin equivalents (LE) and free radicalscavenging activity (FRSA) of herbal tea extracts (after Bhebhe et al. [10]).

    Plant species TPC g GAE/100 g Tannin content of LE/100 g Percentage FRSA IC50g/mL

    Lippia javanica 12.46 ± 4.31 0.12 ± 0.01 83.77 ± 0.8 0.016Aspalathus linearis 6.69 ± 0.83 0.94 ± 0.04 67.27 ± 0.25 0.053Adansonia digitata 0.79 ± 0.28 1.69 ± 0.01 43.07 ± 1.0 0.132Fadogia ancylantha 2.88 ± 0.48 0.20 ± 0.12 70.0 ± 0.40 0.051Ficus sycamores 14.02 ± 0.01 1.98 ± 0.12 86.13 ± 0.85 0.009Myrothamnus flabellifolius 4.75 ± 0.33 1.04 ± 0.01 80.93 ± 0.75 0.019

    41 in Appendix A, from L. javanica. At least 131 differentclasses of essential oil compounds (compounds 42–172 inAppendices A and B) have been isolated from L. javanica byseveral researchers [3–5, 83, 85, 86, 88–94, 123]. Hutchingsand van Staden [96] isolated a toxic triterpenoid saponin,icterogenin 173, from L. javanica leaves. These differentclasses of essential oil compounds have been associatedwith various therapeutic activities such as anaesthetic,analgesic, anti-inflammatory, antimicrobial, cardiovascular,decongestant, digestive, expectorant, hepatoprotective, andsedative activities as well as stimulant of nervous systemand tonifying effects [132]. Meanwhile flavonoids possessseveral pharmacological properties including antibacterial,anticancer, anti-inflammatory, antioxidant, antiviral, andhepatoprotective effects [133] which play important rolesin human health. Flavonoid such as apigenin 7 is reportedto possess antibacterial [134] and hepatoprotective [135]properties. Apigenin 7 and luteolin 12 are reported to possessanti-inflammatory and analgesic effects [133], affecting thefunction of enzyme systems involved in the generation ofinflammatory processes, especially tyrosine and serine-threonine protein kinases [136, 137]. It has also been reportedthat apigenin 7 prevents HIV-1 activation via a novelmechanism that involves inhibition of viral transcription[138] and luteolin 12 demonstrated synergistic effects withanother flavonoid kaempferol against herpes simplex virus[133]. Kamiya [139] documented the importance of essentialamino acids such as lysine, valine, isoleucine, and histidinein terms of the risks to health if they are deficient.The authoralso documented their biological effects which includemuscle protein maintenance, potentiation of immunefunction, tissue repair acceleration after burn or trauma,protecting liver from toxic agents, lowering blood pressure,modulating cholesterol metabolism, and stimulating insulinor growth hormone secretion. Therefore, L. javanica leavesand other plant parts which have shown to be rich inflavonoid and polyphenolic compounds, amino acids, andessential oil could play an important role in the treatmentand management of diseases such as hypertension andinflammation listed in Table 1.

    4. Pharmacological Activities

    Scientific studies on L. javanica indicate that it has a widerange of pharmacological activities (Table 4), which include

    anticancer [140], antidiabetic [141], antimalarial [4, 49, 142],antimicrobial [2, 3, 7, 17, 73–75, 77, 83, 84, 126, 143],antioxidant [7, 10, 11, 75, 77, 125], antiplasmodial [2, 79,80, 84, 144, 145], and pesticidal effects [1, 2, 59, 95, 120,146–150] and cytotoxicity [2, 73, 79, 120] activities. Table 4summarizes some of the pharmacological studies undertakenon L. javanica extracts aimed at evaluating some of theethnomedicinal uses of the species documented throughoutits distributional range (see Table 1). Some of the listedpharmacological activities may not relate directly to thedocumented ethnomedicinal uses of the species but mayprovide some insight into the species’ potential therapeuticvalue and bioactive properties and application.

    4.1. Anticancer Activity. Fouche et al. [140] reported anti-cancer activity of dichloromethane root extract of L. javanicaagainst three human cells, exhibiting TGI value of 1.82𝜇g/mLfor breast MDA-MB-435, 1.86 𝜇g/mL for breast MDA-N, and2.09 𝜇g/mL for melanoma MALME-3M. Based on literature,a couple of terpenoid compounds that have been isolatedfrom L. javanica are known to have antitumor properties.For example, linalool 120 is known to have antitumoractivity which plays a protective role against hepatotoxicityand the compound has anti-inflammatory activities as well[151]. Research by Yang et al. [152] showed limonene 92 tohave inhibitory effect on pancreatic and mammary tumors.Another terpenoid compound, 𝛼-pinene 44, is known toinhibit translocation of NF-𝜅B or p65 protein into nuclei ofLPS-stimulated THP-1 cells [153]. These findings serve as ascientific validation for the use of L. javanica as a componentof a herbal concoction known in KwaZulu Natal province as“imbiza,” prepared by mixing L. javanica with C. obliquus asherbal medicine for cancer [27].

    4.2. Antidiabetic Activity. Arika et al. [141] determined the invivo antidiabetic activity of aqueous leaf extracts of L. javan-ica in white male alloxan-induced albino mice. The aqueousleaf extracts of L. javanica at all dose levels significantlylowered the blood glucose levels in both oral and intraperi-toneal routes. The antidiabetic effect of L. javanica couldhave been due to the observed presence of flavonoids. Thepolyhydroxylated flavonol enhances lipogenesis and glucoseuptake in the adipocytes and flavanoids have demonstratedinsulinmimetic properties as the compound is known to beeffective at controlling blood sugar levels. These findings

  • 12 Evidence-Based Complementary and Alternative Medicine

    Table4:Summaryof

    pharmacologicalactiv

    ities

    ofthee

    xtractsisolated

    from

    different

    partso

    fLippiajavanica.

    Activ

    ityteste

    dEx

    tract

    Plantp

    art

    Mod

    elEff

    ect

    Reference

    Antiamoebic

    Piperitenon

    e162

    Leaves

    Microdilutio

    nassay

    Activ

    ewith

    IC50valueo

    f25𝜇

    g/mLagainstE

    .histolytica

    [73]

    Antibacteria

    lPiperitenon

    e162

    Leaves

    Microdilutio

    nassay

    Activ

    ewith

    MIC

    valueo

    f50𝜇

    g/mLagainstA

    .calcoaceticu

    s,M.kristin

    ae(50𝜇

    g/mL),S.typhi(25𝜇

    g/mL),and

    S.aureus

    (12𝜇

    g/mL)

    [73]

    Antibacteria

    l(Antiproteus)

    Methano

    lLeaves

    Disc

    diffu

    sion

    assay

    Activ

    ewith

    MIC

    valueo

    f313𝜇g/mLagainstP.m

    irabilis

    and926𝜇

    g/mL

    againstP.vulgaris

    [74]

    Water

    Leaves

    Disc

    diffu

    sion

    assay

    Exhibitedweakactiv

    ityagainstP.m

    irabilis

    with

    MIC

    valueo

    f1873𝜇g/mLand1768𝜇g/mLagainstP.vulgaris

    [74]

    Antibacteria

    l

    Aceton

    eLeaves

    Microdilutio

    nassay

    Activ

    eagainstE.

    coliwith

    MIC

    valueo

    f0.64m

    g/mL,E.

    faecalis(0.64),P.

    aeruginosa

    (0.32

    ),andS.aureus

    (0.64).Totalactiv

    ityMIC

    values

    werea

    sfollo

    ws:E.

    coli(127

    mg/mL),E

    .faecalis

    (127

    mg/mL),P.aeruginosa

    (253

    mg/mL),and

    S.aureus

    (127

    mg/mL)

    [75]

    Aceton

    eLeaves

    Microdilutio

    nassay

    Activ

    eagainstB.

    cereus

    with

    MIC

    valueo

    f3mg/mL,Ba

    cillusp

    umilu

    s(6

    mg/mL),B

    .subtilis(>12mg/mL),S.aureus(12mg/mL),E

    .faecalis

    (6mg/mL),E

    .cloacae

    (6mg/mL),E

    .coli(6m

    g/mL),Pantoea

    agglo

    meran

    s(12mg/mL),P.aeruginosa(12m

    g/mL),Shigella

    flexneri

    (1.5mg/mL),A

    erom

    onas

    hydrophila(12m

    g/mL),P.m

    irabilis

    (>12mg/mL),K

    .pneum

    oniae(12mg/mL),Salmonellacholeraesuis

    (6mg/mL),and

    Serratiamarcescens(>12mg/mL)

    [17]

    Hexane

    Leaves

    Microdilutio

    nassay

    Activ

    eagainstB.

    cereus

    with

    MIC

    valueo

    f12m

    g/mL,B.

    pumilu

    s(12m

    g/mL),B

    .subtilis(12m

    g/mL),S.aureus(6m

    g/mL),E

    .faecalis

    (12m

    g/mL),E

    .cloacae

    (12m

    g/mL),E

    .coli(6m

    g/mL),P.agglomeran

    s(12m

    g/mL),P.aeruginosa(12m

    g/mL),S.flexneri(6

    mg/mL),A

    .hydrophila(12m

    g/mL),P.m

    irabilis

    (12m

    g/mL),K

    .pneum

    oniae

    (12m

    g/mL),S.choleraesuis(6

    mg/mL),and

    antia

    moebice

    ffect

    (12m

    g/mL)

    [17]

    Methano

    lLeaves

    Microdilutio

    nassay

    Activ

    eagainstB.

    cereus

    with

    MIC

    values

    of1.5

    mg/mL,B.

    pumilu

    s(6

    mg/mL),B

    .subtilis(>12mg/mL),S.aureus(12mg/mL),E

    .faecalis

    (3mg/mL),E

    .cloacae

    (6mg/mL),E

    .coli(6m

    g/mL),P.agglomeran

    s(12m

    g/mL),P.aeruginosa(12m

    g/mL),S.flexneri(1.5mg/mL),A

    .hydrophila(6

    mg/mL),P.m

    irabilis

    (>12mg/mL),K

    .pneum

    oniae

    (12m

    g/mL),S.choleraesuis(6

    mg/mL),and

    S.marcescens(12mg/mL)

    [17]

    Essentialoil

    Leaves

    Microdilutio

    nassay

    Activ

    eagainstB.

    cereus

    with

    MIC

    values

    of6m

    g/mL,B.

    pumilu

    s(6

    mg/mL),B

    .subtilis(3mg/mL),S.aureus(1.5

    mg/mL),E

    .faecalis

    (3mg/mL),E

    .cloacae

    (12m

    g/mL),E

    .coli(6m

    g/mL),P.agglomeran

    s(6

    mg/mL),P.aeruginosa(12m

    g/mL),S.flexneri(3mg/mL),A

    .hydrophila(3mg/mL),P.m

    irabilis

    (>12mg/mL),K

    .pneum

    oniae

    (3mg/mL),S.choleraesuis(1.5mg/mL),and

    S.marcescens(>12mg/mL)

    [17]

  • Evidence-Based Complementary and Alternative Medicine 13

    Table4:Con

    tinued.

    Activ

    ityteste

    dEx

    tract

    Plantp

    art

    Mod

    elEff

    ect

    Reference

    Methano

    lLeaves

    Microdilutio

    nassay

    Activ

    eagainstE.

    faecaliswith

    MIC

    valueo

    f0.14

    mg/mL

    [7]

    Methano

    lLeaves

    Microdilutio

    nassay

    Activ

    eagainstE.

    coliwith

    MIC

    valueo

    f0.31

    mg/mL

    [7]

    Methano

    lLeaves

    Microdilutio

    nassay

    Activ

    eagainstP.aeruginosa

    with

    MIC

    valueo

    f0.42m

    g/mL

    [7]

    Methano

    lLeaves

    Microdilutio

    nassay

    Activ

    eagainstS.aureus

    with

    MIC

    valueo

    f0.13

    mg/mL

    [7]

    Antifu

    ngal

    Aceton

    eLeaves

    Microdilutio

    nassay

    Activ

    eagainstC.

    albicans

    with

    MIC

    valueo

    f>7.5m

    g/mL,C.

    krusei

    (1.88m

    g/mL),and

    C.neoforman

    s(>7.5

    mg/mL)

    [7]

    Hexane

    Leaves

    Microdilutio

    nassay

    Activ

    eagainstC.

    albicans

    with

    MIC

    valueo

    f>3.75

    mg/mL,C.

    krusei

    (3.75m

    g/mL),and

    C.neoforman

    s(>7.5

    mg/mL)

    [7]

    Aceton

    eLeaves

    Microdilutio

    nassay

    Activ

    eagainstC.

    kruseiwith

    MFC

    valueo

    f7.5mg/mL

    [7]

    Dichlorom

    ethane

    Aeria

    lparts

    Microdilutio

    nassay

    Activ

    eagainstFu

    sariu

    mproliferatum

    with

    MIC

    valueo

    f0.14

    mg/mLand

    Fusariu

    mverticillioides(0.19mg/mL)

    [76]

    Hexane

    Aeria

    lparts

    Microdilutio

    nassay

    Activ

    eagainstF.proliferatum

    with

    MIC

    valueo

    f0.23m

    g/mLandF.

    verticillioides(0.45

    mg/mL)

    [76]

    Methano

    lAe

    rialp

    arts

    Microdilutio

    nassay

    Activ

    eagainstF.proliferatum

    with

    MIC

    valueo

    f1.77m

    g/mLandF.

    verticillioides(0.43

    mg/mL)

    [76]

    Methano

    lAe

    rialp

    arts

    Microdilutio

    nassay

    Activ

    eagainstF.proliferatum

    with

    MIC

    valueo

    f>2.50

    mg/mLandF.

    verticillioides(>2.50

    mg/mL)

    [76]

    Antim

    ycob

    acteria

    l

    Aceton

    eLeaves

    Microdilutio

    nassay

    Activ

    ewith

    MIC

    valueo

    f0.47m

    g/mLandtotalactivity

    of10mL/g

    againstM

    .smegmatis

    [77]

    Dichlorom

    ethane

    Leaves

    Microdilutio

    nassay

    Activ

    ewith

    MIC

    valueo

    f1.25m

    g/mLandtotalactivity

    of23

    mL/g

    againstM

    .smegmatis

    [77]

    Hexane

    Leaves

    Microdilutio

    nassay

    Activ

    ewith

    MIC

    valueo

    f0.62m

    g/mLandtotalactivity

    of13mL/g

    againstM

    .smegmatis

    [77]

    Methano

    lLeaves

    Microdilutio

    nassay

    Activ

    ewith

    MIC

    valueo

    f1.25m

    g/mLandtotalactivity

    of7m

    L/gagainst

    M.smegmatis

    [77]

  • 14 Evidence-Based Complementary and Alternative Medicine

    Table4:Con

    tinued.

    Activ

    ityteste

    dEx

    tract

    Plantp

    art

    Mod

    elEff

    ect

    Reference

    Antioxidant

    Water

    Leaves

    DPP

    Hassay

    Exhibitedactiv

    itywith

    EC50valueo

    f358𝜇g/mL

    [7]

    Water

    Leaves

    —Ex

    hibitedactiv

    itywith

    209ascorbicacid

    equivalent

    (mg/gdryweight)

    [7]

    Water

    Leaves

    ABT

    Sassay

    Activ

    ewith

    TEAC

    valueo

    f1.5mmol/10

    0g[78]

    Water

    Leaves

    DPP

    Hassay

    Activ

    ewith

    TEAC

    valueo

    f1462.54

    mmol/10

    0g[78]

    Water

    Leaves

    FRAPassay

    Activ

    ewith

    TEAC

    valueo

    f2.38m

    mol/10

    0g[78]

    Antiplasm

    odial

    Hexane,chloroform

    Roots

    Microdilutio

    nassay

    Activ

    eagainstP.falciparum

    chloroqu

    ines

    ensitivew

    ithIC50valueo

    f12.25±0.72𝜇g/mL

    [79]

    Ethylacetate

    Roots

    Microdilutio

    nassay

    Activ

    eagainstP.falciparum

    chloroqu

    ines

    ensitivew

    ithIC50valueo

    f12.12±0.79𝜇g/mL

    [79]

    Methano

    lRo

    ots

    Microdilutio

    nassay

    Activ

    eagainstP.falciparum

    chloroqu

    ines

    ensitivew

    ithIC50valueo

    f1.35±0.06𝜇g/mL

    [79]

    Hexane,chloroform

    Roots

    Microdilutio

    nassay

    Activ

    eagainstP.falciparum

    chloroqu

    iner

    esistantw

    ithIC50valueo

    f18.59±0.26𝜇g/mL

    [79]

    Ethylacetate

    Roots

    Microdilutio

    nassay

    Activ

    eagainstP.falciparum

    chloroqu

    iner

    esistantw

    ithIC50valueo

    f15.80±0.26𝜇g/mL

    [79]

    Methano

    lRo

    ots

    Microdilutio

    nassay

    Activ

    eagainstP.falciparum

    chloroqu

    iner

    esistantw

    ithIC50valueo

    f1.75±0.17𝜇g/mL

    [79]

    Dichlorom

    ethane

    Roots

    pLDHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f3.8𝜇g/mL

    [80]

    Dichlorom

    ethane/m

    ethano

    lRo

    ots

    pLDHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f27𝜇

    g/mL

    [80]

    Methano

    lRo

    ots

    pLDHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f24𝜇

    g/mL

    [80]

    Water

    Roots

    pLDHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f>100𝜇

    g/mL

    [80]

    Dichlorom

    ethane

    Stem

    spL

    DHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f4.5𝜇g/mL

    [80]

    Dichlorom

    ethane/m

    ethano

    lStem

    spL

    DHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f21.8𝜇g/mL

    [80]

    Methano

    lStem

    spL

    DHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f29.8𝜇g/mL

    [80]

    Water

    Stem

    spL

    DHassay

    Activ

    eagainstP.falciparum

    with

    IC50valueo

    f>100𝜇

    g/mL

    [80]

    Free

    radicalscaveng

    ing

    activ

    ity

    Water

    —DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.059±0.02

    g/mL

    [11]

    50%methano

    l—

    DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.04±0.001g/mL

    [11]

    Ethano

    l—

    DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.025±0.001g/mL

    [11]

    50%ethano

    l—

    DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.027±0.005g/mL

    [11]

    Aceton

    e—

    DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.057±0.004g/mL

    [11]

    50%aceton

    e—

    DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.022±0.001g/mL

    [11]

    Ethylacetate

    —DPP

    Hassay

    Activ

    ewith

    IC50valueo

    f0.066±0.001g/mL

    [11]

    Toxicity

    Methano

    lLeaf

    Brines

    hrim

    plethality

    assay

    40%mortalityrecorded

    after

    48hexpo

    sure

    towards

    Artemianauplii

    [74]

    Methano

    lRo

    ots

    Brines

    hrim

    plethality

    assay

    Activ

    eagainstP.falciparum

    chloroqu

    ines

    ensitivew

    ithIC50valueo

    f843.0𝜇

    g/mL

    [79]

    Methano

    lRo

    ots

    Brines

    hrim

    plethality

    assay

    Activ

    eagainstP.falciparum

    chloroqu

    iner

    esistantw

    ithIC50valueo

    f650.3𝜇

    g/mL

    [79]

  • Evidence-Based Complementary and Alternative Medicine 15

    strengthen the view that L. javanica is a potential source ofantidiabetic agents and to some extent validate the traditionaluse of the plant species mixed with C. obliquus to form aherbal concoction known in KwaZulu Natal province, SouthAfrica, as “imbiza” used against diabetes [27].

    4.3. Antimalarial Activity. Govere et al. [142] found thattopical application of L. javanica alcohol extract leads to76.7% protection against Anopheles arabiensis for 4 hours.Lippia javanica has been used as a mosquito repellent by therural communities in Zimbabwe for a long time and previousstudies have shown that essential oils from the species havevery strong and lasting repellent activity against female A.arabiensis [64]. Research by Lukwa et al. [4] revealed thattopical application of 5mg/cm2 of L. javanica leads to 100%protection againstAnopheles aegypti for 8 hours.Mavundza etal. [154] screened dichloromethane and ethanol leaf extractsof L. javanica for adulticidal activity againstA. arabiensis.Theauthors observed dichloromethane and ethanol activities of45% and 55%mosquitomortality, respectively.These findingsstrengthen the view that L. javanica is a potential source ofantimalarial agents and to some extent validate the traditionaluse of the plant species as mosquito repellent in India [47],South Africa [34, 49, 58], and Zimbabwe [4, 48].

    4.4. Antioxidant Activity. Leaf infusions of L. javanica exhib-ited antioxidant activity with EC

    50value of 358𝜇g/mL and

    contained 14.8mg/mL of dry weight gallic acid equivalentphenolic compounds [7]. The EC

    50value of 358 𝜇g/mL

    obtained for L. javanica by Shikanga et al. [7] compareswell to those of many commercial teas, including antioxidantcapacity of Rooibos Fresh Pack� herbal teas (A. linearis)with the best antioxidant activity of 333 𝜇g/mL. The highantioxidant activities displayed by L. javanica infusions canbe partially attributed to the high levels of verbascoside 2(1.5mg/g dry weight) reported by Olivier et al. [81] in theleaf extract of the species. Earlier research by Muchuwetiet al. [125] reported 74.4% inhibition of the DPPH radicalby an ethanolic leaf extract of L. javanica. Lekganyane etal. [75] reported antioxidant activity in L. javanica and theacetone extracts of the species displayed antioxidant activityon BEA chromatogram [77]. Bhebhe et al. [10] reported theantioxidant activities of L. javanica based on the DPPH,reducing power and inhibition of phospholipid peroxidationassays. Free radical scavenging activity of L. javanica isattributed to phenolic compounds since these compoundshave an ideal structural chemistry for free radical scavengingactivity [155]. Bhebhe et al. [11] determined the effect ofseveral solvents on the free radical scavenging activity ofL. javanica using the DPPH assay. Free radical scavengingactivity expressed as IC

    50ranged from 0.022 ± 0.001 g/mL to

    0.066 ± 0.001 g/mL; see Table 4.

    4.5. Antiplasmodial Activity. Prozesky et al. [144] evaluatedL. javanica leaf acetone extract for in vitro antiplasmodialactivity using PfUP1, a chloroquine resistant strain of themalaria parasite Plasmodium falciparum by means of theflow cytometric test. The IC

    50value for L. javanica was

    4.26 𝜇g/mL. Manenzhe et al. [2] evaluated essential oil,

    piperitenone 162, isolated from L. javanica for antiplasmodialactivity using chloroquine diphosphate as positive controland found it active against a chloroquine sensitive strainof P. falciparum in micromolar concentrations with IC

    50of

    8 𝜇g/mL. Clarkson et al. [80] evaluated L. javanica rootsand stems extracts for in vitro activity against P. falciparumusing the parasite lactase dehydrogenase (pLDH) assay andchloroquine diphosphate (Sigma) as the positive control.Thedichloromethane, methane, and water extracts showed IC

    50

    values ranging from 3.8 to >100 𝜇g/mL; see Table 4. Omolo etal. [145] screened the essential oil of L. javanica for fumiganttoxicity to Anopheles gambiae which exhibited LD

    50of 4.3 ×

    10−3mg cm−3. Ayuko et al. [79] showed that L. javanica rootextracts have antiplasmodial activity against P. falciparumwith IC

    50ranging from 1.35 to 18.59 𝜇g/mL; see Table 4.

    Lippialactone 21, derived from the ethyl acetate extract ofaerial parts of L. javanica, exhibited some activity againstthe chloroquine sensitive D10 strain of P. falciparum withan IC

    50value of 9.1 𝜇g/mL and is also mildly cytotoxic [84].

    Compared to chloroquine, the compound is approximately2000 times less active against the D10 strain of P. falciparum[84].

    4.6. Antimicrobial Activities. Lippia javanica is widely usedin the treatment of a wide range of infectious diseasescaused by microorganisms. Viljoen et al. [3] determined theantimicrobial properties of L. javanica by evaluating the timekill studies of the species’ essential oil using the disc diffusionassay on three respiratory pathogens Klebsiella pneumoniae,Cryptococcus neoformans, and Bacillus cereus. This studyshowed that the killing rate was greatest for K. pneumoniaefollowed by C. neoformans and very little reduction of micro-bial populations was observed for B. cereus. The efficacy of L.javanica oil for K. pneumoniae showed a killing rate within30 minutes for the concentrations 0.25, 0.5, 0.75, and 1%,C. neoformans showed a killing rate for concentrations 0.5,0.75, and 1% within 1 hour, and the lowest concentration of0.25% took 8 hours before a bactericidal effect was notedwhile B. cereus showed some reduction in colonies [3]. Thepositive antimicrobial activity of L. javanica as revealed bythe time kill study could be attributed to linalool 120 whichaverages between 65 and 70% in yield [3, 5, 88, 90] and hasknown antimicrobial properties [93, 156–159].These findingssomehow corroborate the traditional use of L. javanica asherbal medicine for a wide range of bacterial and fungalrespiratory ailments indicated in Table 1.

    Manenzhe et al. [2] evaluated essential oil, piperitenone162, isolated from L. javanica for antibacterial activityon cultures of Bacillus subtilis, Staphylococcus aureus, andEscherichia coli using imipenem, cefazolin, and ampicillinas positive controls. The authors found piperitenone 162to inhibit S. aureus and E. coli at 1% dilution. Acetone,hexane, and methanol leaf extracts and essential oil isolatedfrom L. javanica showed some activity against fifteen Gram-positive and Gram-negative bacteria with MIC values rang-ing from 1.5 to >12mg/mL [60]; see Table 4. In a similarstudy, Samie et al. [73] demonstrated that a pure compoundpiperitenone 162 isolated from L. javanica has antibacte-rial activities against Acinetobacter calcoaceticus, Micrococcus

  • 16 Evidence-Based Complementary and Alternative Medicine

    kristinae, Salmonella typhi, and S. aureus using dimethylsulphoxide and kanamycin as controls, with MIC valuesranging from 12 to 50 𝜇g/mL; see Table 4. Shikanga et al. [7]evaluated the antibacterial activity of L. javanica methanolicleaf extract against S. aureus, Enterococcus faecalis, E. coli,and Pseudomonas aeruginosa using the serial microdilutionmethod with gentamycin (Virbac�) and acetone as positiveand negative controls, respectively. Lippia javanica displayedantibacterial activities with MIC values ranging from 0.13to 0.42mg/mL against all four pathogens; see Table 4. Theobtained minimum inhibitory concentrations are promising,since natural products with MIC values below 1mg/mLare generally considered to be noteworthy findings [160].Lippialactone 21, derived from the ethyl acetate extract ofaerial parts of L. javanica, exhibited some activity against theE. coli and S. aureus at a concentration of 10mg/mL [84].Lekganyane et al. [75] reported antibacterial activity of L.javanica acetone leaf extracts against E. coli, E. faecalis, P.aeruginosa, and S. aureus with MIC values ranging from 0.32to 0.64mg/mL and total activity of the same species rangingfrom 127 to 253mg/mL; see Table 4. Methanol and water leafextracts of L. javanica exhibited some antiproteus activityagainstProteusmirabilis andProteus vulgariswithMICvalues7.5mg/mL;see Table 4. Thembo et al. [76] investigated the antifungalactivity of aqueous and organic extracts of L. javanica usinga serial microdilution assay. Generally, extracts of L. javanicaexhibited weak activity; see Table 4.

    4.7. Antimycobacterial Activity. Mujovo et al. [83] evaluatedL. javanica compounds against a drug-sensitive strain ofMycobacterium tuberculosis using the radiometric respira-tory techniques. Of all the isolated compounds, only onetriterpenoid carboxylic acid, euscaphic acid 172, exhibitedantimycobacterial activity with MIC value of 50𝜇gmL−1against this strain. In a similar study, the leaf extract ofL. javanica exhibited antimycobacterial activity against M.smegmatis in an evaluation which used microdilution assayand rifampicin as control [77]. Acetone extract was thebest extractant with MIC value of 0.47mg/mL; it extractedantibacterial agents which was indicated by the lowest MICvalue [77]. Masoko and Nxumalo [77] also evaluated thetotal activity ofL. javanicawhich averaged 13mL/g suggestingthat the extract prepared from one gram of L. javanicacould be diluted to a volume of 13mL and will still inhibitM. smegmatis efficiently. According to Semenya and Maroyi[115], tuberculosis caused by M. tuberculosis is a seriousdisease requiring effective strategies and tools to controland manage it. Therefore, preliminary evaluations done byMujovo et al. [83] and Masoko and Nxumalo [77] serve asa scientific validation for the use of L. javanica in traditionalmedicine for treatment of tuberculosis and other respiratoryailments in South Africa [24, 27, 115] and Uganda [43] as wellas their efficiency in tuberculosis drug discovery.

    4.8. Antiviral Activity. Mujovo et al. [83] found that (E)-2(3)-tagetenone epoxide 42 and piperitenone 162 inhibitedthe HIV-1 reverse transcriptase enzyme by 91% and 53%,respectively, at 100 𝜇gmL−1 based on a nonradioactive HIVRT colorimetric ELISA kit. Little is known about the HIV RTactivity of L. javanica extracts or compounds, but flavonoidsare known to be active against viral RT and also as potentinhibitors of the cellular alpha and beta DNA polymerase[83], while luteolin 12 is active against HIV RT [164, 165].Lippia javanica is traditionally used to treat HIV/AIDSsymptoms in South Africa [65, 66] and several viral andHIV/AIDS opportunistic diseases and infections such asbronchitis [15, 19–22], chicken pox [50], diarrhoea [17, 34,37, 44, 113], measles [14, 20, 38], pneumonia [14], shingles[15], and venereal diseases [44]. Despite significant advancesin the utilization of L. javanica in southern Africa overthe years for numerous viral diseases (Table 1), very littleantiviral evaluations have been done on crude extracts andpurified compounds of the species. There is need, therefore,for more pharmacological research as L. javanica could beharbouring potent (RT) inhibitors which could be useful forthe development of new pharmaceutical products importantfor use against viral diseases and infections.

    4.9. Pesticidal Effects. Magano et al. [95] evaluated the repel-lent effects of hexane extracts of L. javanica essential oilusing the in vitro tick climbing repellency bioassay on adultsof Hyalomma marginatum rufipes Koch ticks. The authorsfound that 107mg/mL caused repellency index of 100% at onehour and 30 minutes. In a similar study by Madzimure et al.[120], L. javanica aqueous leaf extracts at 10% and 20% w/vwere effective at controlling cattle ticks (Amblyomma species,

  • Evidence-Based Complementary and Alternative Medicine 17

    Boophilus species, Hyalomma species, Rhipicephalus appen-diculatus, and Rhipicephalus evertsi evertsi) and were as goodas the positive control amitraz-based acaricide Trickbuster�.These authors found no parasites on microscopic exami-nation of the Giemsa-stained thin blood smear collectedfrom treated cattle implying that the animals did not sufferfrom clinical tick-borne diseases. Similarly, Nyahangare etal. [59] tested the pesticidal activity of L. javanica waterextracts against cattle ticks. The authors found no significantdifference between cattle treated with a commercial syntheticacaricide and those under L. javanica treatment. Martinez-Velazquez et al. [166] evaluated pesticidal effects of twoessential oils, namely, 𝛾-terpinene 82 and 𝜌-cymene 99,isolated from Lippia graveolens Kunth against 10-day-oldRhipicephalus (Boophilus) microplus (Canestrini) tick larvaeusing the larval packet test bioassay. The two essential oilsproduced highmortality ranging from90 to 100% in all testedconcentrations of 20 to 1.25% (v/v).Therefore, L. javanica canprovide an effective tick control option where synthetic prod-ucts are unavailable or unaffordable particularly in remoterural areas in sub-Saharan Africa. Lippia javanica is popularfor tick control and management among resource-poorsmallholder farmers in South Africa [58, 95] and Zimbabwe[59, 60, 120]. While these preliminary evaluations may serveas confirmation that L. javanica has some bioactivities againstticks, a comprehensive method of tick control is requiredfor the resource-constrained smallholder farmers based onethnopharmacological properties of L. javanica.

    McGaw et al. [146] screened L. javanica for the anthel-mintic test systems using the free living nematodeCaenorhabditis elegans. The crude ethanol and hexaneextracts showed some activity at a concentration of 2mg/mL,with the 7-day incubation assay appearing to be moresensitive than the shorter assay. Earlier research by Mwangiet al. [1] indicated that L. javanica was active against Aedesaegypti larvae and Sitophilus zeamais Motschulsky (maizeweevil). Katsvanga and Chigwiza [147] reported that L.javanica is an effective natural pesticide which can be used tocontrol aphid species (Brevicoryne brassicae). In their study,Katsvanga and Chigwiza [147] found that 1 : 1 powderedaqueous leaf extract of L. javanica reduced B. brassicae by53.2% against 78.3% and 96.7% of two synthetic pesticides,Aphid kill and Bexadust “L,” respectively. Chikukura etal. [149] found L. javanica powdered leaf extracts to haveinsecticidal properties with potential to control graindamage by 21–33%. Mashela et al. [148] reported that theapplication of ground L. javanica leaves to soil in nematode-infested (Meloidogyne incognita) pots reduced the nematodenumbers by 79–92% and significantly increased fresh fruityield, dry shoot mass, plant height, and stem diameter ofthe tomato plants, as well as levels of potassium, nitrogen,and manganese in leaf tissue. Muzemu et al. [150] evaluatedwater extracts of L. javanica leaf powder for pesticidal effectsagainst rape (Brassica napus L.) aphids, B. brassicae, andtomato (Solanum lycopersicum Lam.) red spider mites, andTetranychus evansi as alternatives to conventional pesticides.Lippia javanica reduced B. brassicae and Tetranychus evansiby 12.5% and 63%, respectively [150].The study demonstratedthat L. javanica has pesticidal effects on B. brassicae and T.

    evansi. The reduced number of B. brassicae and T. evansicould be due to L. javanica’s extracts having repellent, toxic,and antifeedant effects since the species has essential oilswith pesticidal properties [2]. Therefore, these findingsindicate that L. javanica has both nematicidal and plantgrowth-promoting properties.

    4.10. Toxicity and Cytotoxicity Activity. Lippia javanica isknown to cause liver damage and photosensitisation in live-stock, resulting in stock losses [167]. Triterpenoids isolatedfrom the genus Lippia are icterogenic and cause jaundice asa result of liver damage [167]. The characteristic swelling,yellowing, and later peeling of unpigmented skin are due tothe presence of phylloerythrin, a photodynamic porphyrinthat reacts with sunlight and causes severe cell damage [167].The compound is normally formed when chlorophyll isbroken down by microorganisms in the rumen, but it nowaccumulates in the liver as a result of the damage caused bytriterpenoids [167]. In view of the known toxicity of Lippiaspecies, the prolonged use of high doses of L. javanica ispotentially harmful [167]. Lippia javanica showed low toxicityafter 48 h exposure with the percentage of mortality below50% [74].

    Ayuko et al. [79] evaluated the toxicity of L. javanicausing a brine shrimp cytotoxicity assay with LC

    50value of

    1138 ± 1.33 𝜇g/mL. Ayuko et al. [79] found the cytotoxicity toantiplasmodial activity ratios for the methanolic extracts ofthe two tested strains to be 843.0 and 650.3, and since theseare greater than 100, it may be concluded that the extractsare of low toxicity. Samie et al. [73] demonstrated that apure compound piperitenone 162 isolated from L. javanicaessential oil has low cytotoxicity activity against intestinaladenocarcinoma cells (i.e., the HCT-8 monolayers with IC

    50

    of 265.6 ± 5.3 𝜇g/mL). Lukwa [64] evaluated the toxicity of L.javanica aqueous leaf extracts using sexually mature BALB/cmice with the placebo as control. Within 48 hours, all micefed with the L. javanica leaf aqueous extract at 12.5–37.5% v/vwere lethargic, and the overall mortality was 37.5%. Previousresearch byManenzhe et al. [2] showed that hydrodistillationof L. javanica leaves, flowers, and stems produced oil thatwas poisonous against P. falciparumwhen diluted to 1% (v/v).These findings imply that, despite its apparent safety, waterextracts of L. javanica leaves may have deleterious healthimplications on humans and animals if consumed at veryhigh doses.

    Many compounds that have been isolated from L. javan-ica including phenolic glycosides, flavonoids, and essentialoils are not known to have acute toxic properties withthe exception of icterogenin 173. Icterogenin 173 has beenshown to inhibit biliary excretion in rabbits [168]. Reports inliterature indicate that the consumption of xanthine 22 hasresulted in mammalian toxicity. According to Madzimure etal. [64], xanthine 22 is a demethylated derivative of caffeinewith pharmacological actions such as central nervous system(CNS) stimulation, relaxation of smooth muscle (especiallybronchial muscle), myocardial stimulation, peripheral vaso-constriction, and diuresis. Considering the widespread useof L. javanica as herbal tea and medicine, it is important

  • 18 Evidence-Based Complementary and Alternative Medicine

    to determine if any toxicological effects can occur from itschronic or subchronic usage.

    4.11. Other Activities. Mpofu et al. [169] determined the effectof inclusion of L. javanica leaf meal in broiler diets ongrowth performance, carcass characteristics, and fatty acidprofiles. The authors found that the L. javanica fed broilershad higher total polyunsaturated fatty acids and n-3 fattyacids.The findings from the study showed that inclusion of L.javanica in broiler diets at 5 g/kg feed has positive influenceson growth performance, carcass characteristics, and fattyacid profiles of broiler meat and, therefore, L. javanica haspotential as growth-promoting feed additive in broilers.Samie et al. [73] evaluated antiamoebic activity of a purecompound piperitenone 162 isolated from L. javanica essen-tial oil against Entamoeba histolytica using microdilutionmethod with metronidazole as the positive control, diluents(i.e., culture medium with an appropriate concentration ofdimethyl sulphoxide as the negative control), and a blank(i.e., culture medium without dimethyl sulphoxide). Samieet al. [73] demonstrated that piperitenone 162 had markedantiamoebic activity with IC

    50value of 25 𝜇g/mL. More

    research is required as L. javanica could be harbouring potentantiamoebic properties which could be useful for managingamoebiasis, an infection that remains a sign