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Turmeric ‐ The choice of millionsTurmeric The choice of millions
“IF MY FATE were such that I could have IF MY FATE were such that I could have
only one medicinal plant, I would choose
turmeric. My choice would be the choice of
millions before me, from emperors to
peasants.” peasants.
C. Leigh Broadhurst, Ph.D
22USDA
33
Turmeric Plant
Curcuma longaCurcuma longa
Herbaceous plant belonging to the familyHerbaceous plant belonging to the familyZingiberaceae.
Useful parts are the underground rhizome and p gmulti‐branched extensions from theRhizomes.Rhizomes.
Spice and Natural color usedSpice and Natural color used globally in curries……….
44
Important constituents of Curcuma longaImportant constituents of Curcuma longa
CurcuminDemethoxy curcuminBi d th iBisdemethoxy curcuminTurmeronesTurmerones
55
Chemical structures of Curcuminoids
M O OM
CH CHCOCH CO CHCHOH
MeO
OH
OMe
CURCUMIN (Diferuloyl methane)
CH CHCOCH2CO CHCHOH OH
CURCUMIN ( f y )
OMe
CH CHCOCH2CO CHCHOH OH
DEMETHOXY CURCUMIN (p‐Hydroxy‐cinnamoyl‐feruloyl‐methane )
66
Chemical structures of CurcuminoidsChemical structures of Curcuminoids
CH CHCOCH2CO CHCHOH OH
BISDEMETHOXY CURCUMIN (pp’ Dihydroxy dicinnamoyl methane)(pp ‐Dihydroxy‐dicinnamoyl‐methane)
CH3
CH
CH3
CHO
ar‐turmerone
CH3 CH3O
77
Curcumin C3 Complex
fromfrom
Turmeric RhizomesTurmeric Rhizomes
88
The structure – activity relationshipThe structure activity relationship
OO 22
CH C CH2 C CH33
CHCH
OMeMeO
1 P h d l ti id t ti it
OHOH1 1
1.Parahydroxyl groups ‐ antioxidant activity2.Keto groups ‐ anti‐inflammatory, anticancer, antimutagen3.Double bonds ‐ anti‐inflammatory, anticancer, antimutagen
99f y, , g
Primary pharmacological actions of Curcuminoidsy p g
AntioxidantAnti‐inflammatoryAnti‐carcinogenicAnti‐carcinogenicImmunomodulatoryA ti t iAntimutagenicAnti‐thromboticHepatoprotectantAntimicrobialAntiviralAntiparasitic
1010Antiparasitic
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Antioxidant Profile – Rancimat Test
IN VITRO
The Rancimat Method measures the conductivity changes caused by formation of small free fatty acid molecules, when fats and oils undergo experimentally induced accelerated rancidity or oxidative changes.
Pure lard is used for the preparation of test samples % b h f h d bcontaining 0.02% by weight of the antioxidant being
tested.
1212‐‐ContdContd..
Lipid peroxidation prevention by natural and synthetic i id d b R i M h d
Research report no. 786, Sabinsa Corporation, 1995
antioxidants as measured by Rancimat Method
3
xResearch report no. 786, Sabinsa Corporation, 1995
2
2.5
t inde
1.5
xidant
0.5
1
Antiox
0
1 2 3 4 5 6
A
1. BHT 2. Curcumin 3. BDMC
4 Cu u i C3 5 G a e Seed 6 Pi e Ba k1313
4. Curcumin C3 Complex
5. Grape Seed Extract
6. Pine Bark Extract
Antioxidant Profile – DPPH Scavengingg g
In the DPPH radical scavenging method, the ability f ti id t t bi d th 1 1 di h l 2of an antioxidant to bind the 1,1 diphenyl‐2‐
picrylhydrazyl ‐radical (a very stable free radical species) is measured, using various concentrations of the selected antioxidants.
A compound with high antioxidant potentialA compound with high antioxidant potential effectively traps this radical thereby preventing its propagation and the resultant chain reactionpropagation and the resultant chain reaction.
1414
DPPH scavenging ability of Curcuminoidssca e gi g abi ity o Cu cu i oids
Concentration (μg/ml)
1515Research Report No. 786, Sabinsa Corporation, 1995
Antioxidant Profile – ORAC value
The Oxygen Radical Absorbance Capacity (ORAC) yg p y ( )assay depends on the free radical damage to a fluorescent probe through the change in itsfluorescent probe through the change in its fluorescence intensity.
In the presence of antioxidant, the inhibition of free di l d hi h i fl t d i th t tiradical damage, which is reflected in the protection
against the change of probe fluorescence, is a measure of its antioxidant capacity against the free radical.
1616
ORAC value of CurcuminoidsORAC value of Curcuminoids
12000
10000
6000
8000
4000
0
2000
Coffee Bean Extract
Curcumin C3 Complex
Grape Seed Extract
Green tea Extract
1717Research Report No. 786, Sabinsa Corporation, 1995
Proposed antioxidant mechanismsProposed antioxidant mechanisms
PREVENTION f f di l f tiPREVENTION of free radical formation.
INTERVENTION whereby already preformedradicals are quenched by the Curcuminoids.q y
1818
1919
Saga of InflammationSaga of Inflammation
Almost all of the degenerative diseases are d i b h i b li i l i fl tidriven by chronic subclinical inflammation.
Essentially, nearly every condition that walks into a doctor’s office is driven at least in part byinto a doctor s office is driven, at least in part, by inflammation.
Co td2020
Contd……
Saga of InflammationSaga of Inflammation
The old view of the inflammation is that it represents the healing process This is true to arepresents the healing process. This is true to a certain extent; however when the inflammation, b h i it b dibecomes chronic, it becomes a disease.
Literature strongly recommends that there is a need to halt the chronic inflammation and itsneed to halt the chronic inflammation and its induction.
Co td2121
Contd……
Saga of InflammationSaga of Inflammation
Today the study of inflammation has gone fromToday the study of inflammation has gone from the tissue levels deeper into the nuclear level.
Cell‐signaling molecules have been identified g gwhich stimulate the gene that induce the expression of the COX enzyme which in turnexpression of the COX enzyme which in turn induce inflammation.
2222
TIME Feb. 23, 2004
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Nuclear factor Kappa B (NF kB)Nuclear factor Kappa B (NF‐kB)
NF kB i th “Bi h ” ll i liNF‐kB is the “Big cheese” cell‐signaling molecule for inflammation;
its activation induces the expression of COX 2its activation induces the expression of COX‐2, which leads to tissue inflammation.
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What activates NF kB?What activates NF‐kB?
ROI inducersCarcinogens
ACytokines
f l I
ROI inducers(H2O2)
( eg: TNF, CSC, DMBA)(TNF family, IL‐1, IL‐17, IL‐18, EGF)
NF-κBTumor
PromotersInfectionb l/ l (PMA)(bacterial/viral; e.g HIV, EBV‐LMP,HTLV1)
Stress(pH, hypoxia,stress
h l )Apoptosis inducers heavy metals)
Endotoxin(LPS)
Apoptosis‐inducersChemotherapeutic
agents & g‐irradiation
25(LPS)
Aggarwal BB, Cancer Cell, 2004
25
NF kB i I fl tiNF‐kB in Inflammation
NF‐kB resides in the cytoplasm of the cell and is bound to its inhibitorbound to its inhibitor.
I j i d i fl t ti li h fInjuries and inflammatory stimuli, such as free radicals, release NF‐kB from its inhibitor.
The free NF‐kB, now moves into the nucleus and ti t th ibl f iactivates the genes responsible for expressing
COX‐2.
This leads to inflammation.2626
Stress and NF‐kBe a
Stress and carcinogens activate NF kBStress and carcinogens activate NF‐kB.
Ch i NF kB i i di i fl i /Chronic NF‐kB activation mediates inflammation/ carcinogenesis/ tumorigenesis .
Inhibition of NF‐kB activation suppresses ppinflammation/ tumorigenesis.
2727
Central dogma for most type of inflammationsCentral dogma for most type of inflammations
TNF/CarcinogensTNF/CarcinogensTNF/CarcinogensTNF/Carcinogens
NF‐kB
COXCOX‐‐222828
Drug‐discovery from natural sourcesDrug‐discovery from natural sources
There are 121 prescription drugs in use today, which come from 90 plant species. About 74% came from following folklore claims. g
(Benowitz S, The Scientist 10, 1996, 1‐7).
Approximately 25% of the drug prescription in the USA are compounds derived from plants and were p pdiscovered through scientific investigation of folklore claimsfolklore claims .
(Reynold T, J. Natl. Cancer Inst. 183, 1991, 594‐596).2929
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Therapeutic potential of curcuminTherapeutic potential of curcuminC di l di
Di b t
Cardiovasuclar diseasesCholestrol, platelet aggregation, inhibition of smooth muscle cell
proliferation
Multiple sclerosis Alzheimer
diseaseDiabetes
ChemotherapeuticNephrotoxicity
C
ChemopreventiveSkin, liver, colon, stomach
Antioxidant
p y
CurcuminAntiflammatory
Gall‐stones
Arthritisformation
Lung fibrosisCataract formation
31Cardiotoxicity
Wound healingHIV replication 31
Different stages of cancer progression and its suppression by curcumin
Overexpression ofOncogenes HER2 Overexpression ofGrowth factors
(e.g; EGF, PDGF, FGF)Growth factor receptorsSurvival factors
( S i i B l 2 d B l l)
Overexpression ofMatrix metalloproteasesCyclooxygenase‐2Adhesion moleculesChemokine
Tumor Suppressor genes
Constitutive activation of transcription factors
AP‐1& NF‐kB(e.g; Survivin,Bcl‐2 and Bcl‐xl) Cyclin D1Decoy receptor
TNF
Tumor MetastasisNormal cells Tumor cells Tumor growth
Proliferation InvasionTransformation
32Curcumin BlocksFrom Aggarwal B et al, Anticancer Research 23, 2003, 363-398
32
Curcumin helps fights diseasesCurcumin helps fights diseases…..
So if we take care to reduce the NF‐kB ti it t ti l factivity, we are protecting ourselves from
a host of diseases, including Cancer.
Cu u i ha a o iti e ole i thiCurcumin has a positive role in this.
K. Kohli, J. Ali, M. J. Ansari, Z. Raheman Curcumin: A natural anti‐inflammatory agenty gIndian J Pharmacol | June 2005 | Vol 37 | Issue 3 | 141‐147( and references cited therein)
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NFkB‐Zero™NFkB Zero
Inhibition of NF‐kB can help prevent/delay the onset ofthe disease.
This is the basic premise on which NFkB‐Zero™ haspbeen developed.
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Effect of curcuminoids application in patients with external cancerous lesions
100
* 62 Subject Study
708090
100
n
506070
educ
tion
203040
% r
e
010
Reduction in fould f l i
Drying lesions Reduction in lesioni d i
Itching
35odor of lesions size and pain
Ref: Kuttan et al., (1987) Tumori, 2, 28-29.
Effect of turmeric administration on levels of urinary mutagensEffect of turmeric administration on levels of urinary mutagens in smokers
300
350
Load
28.5% decrease
(p < 0.001) 40% decrease
200
250
utag
en L 40% decrease
(p < 0.001)
100
150
200
nary
Mu
50
100
Urin
00 15 days 30 days
Time elapse from turmeric administration 16 smokers36
Time elapse from turmeric administration 16 smokers + 6 non-smokers
Ref: Polasa, et al., Mutagenesis, 7, 107 (1992)
D d d t tith b ti ff t f i
Antithrombotic activity of curcumin
Dose dependent antithrombotic effect of curcumin and aspirin
60708090
tion
2030405060
prot
ect
Curcumin
Aspirin
* Platelet0
1020
15 25 50 100 200
% Platelet
aggregation
* PGI2Dose mg/kg PGI2synthesis
37Srivastava, R. et al. (1985) . Thrombosis Res., 40, 413-417.
Effect of curcuminoids on the hepatotoxicity produced by Aflatoxin B1 (AFB) in ducklings
2.5
ty
1.5
2
T ac
tivit
0.5
1
ver G
PT 1 2 3
0
0.5
Liv
1. Normal 2. AFB 3. AFB + Curcuminoids
Treatment regimens38
Treatment regimensSoni et. al. (1992), Cancer Lett, 66, 115
3939
Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials
Since the first article referring to the use of curcumin was published in “The Lancet in 1937” more than 2 600published in The Lancet in 1937 , more than 2,600 research studies using curcumin or turmeric have been published in English language journalspublished in English language journals.
Thi i ti l id i f th t iThis review article provides an overview of the extensive published literature on the use of curcumin as a therapy for malignant and inflammatory diseases and its potentialfor malignant and inflammatory diseases and its potential use in the treatment of degenerative neurologic diseases, cystic fibrosis and cardiovascular diseasescystic fibrosis and cardiovascular diseases.
4040Strimpakos AS, Sharma RA., Antioxid Redox Signal. 2008 Mar; 10(3); 511‐545Department of Medicine, Royal Marsden Hospital, London, England
Curcumin C3 Complex® and Cancer PreventionCurcumin C Complex and Cancer Prevention
41414141
Curcumin C3 Complex® and Cancer PreventionCurcumin C Complex and Cancer Prevention
M.D. Anderson Cancer Center is currently conducting numerous studies to determine the effects of curcumin, an extract of turmeric root, in fighting against several
ftypes of cancers.
S bi C ti ʹ C i C3 C l ®Sabinsa Corporationʹs Curcumin C3 Complex® was named as the curcumin ingredient of choice by M.D. A de o Ca e Ce te at the U i e ity of Te aAnderson Cancer Center at the University of Texas.
42424242
Curcumin Analogues in Cancer PreventionCurcumin Analogues in Cancer Prevention
In a pre‐clinical study, the authors investigated whether analogs of curcumin (Cur), such as demethoxy curcuminanalogs of curcumin (Cur), such as demethoxy curcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC) and turmerones, modulate y ( ) ,inflammatory signaling and cell proliferation to the same extent as curcumin.
The results demonstrated that different analogs ofThe results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti‐inflammatory and anti‐proliferative activities.inflammatory and anti proliferative activities.
4343Sandur SK, Aggarwal BB et al, Carcinogenesis. 2007 Aug; 28(8); 1765‐1773
Curcuminoids and their analogues on production of ll l ROS d GSHcellular ROS and GSH
44cSandur SK, Aggarwal BB et al, Carcinogenesis. 2007 Aug; 28(8); 1765‐1773
44
Comparison of Cancer Incidence ‐1U.S [curcumin non‐users] vs. India [curcumin users]
Cancer US IndiaCancer US IndiaCases Deaths Cases Deaths
Breast 600 160 79 41Breast 600 160 79 41Prostate 690 130 20 9Colon/Rectum 530 220 30 18Colon/Rectum 530 220 30 18Lung 660 580 38 37Head and Neck SCC 140 44 153 103Head and Neck SCC 140 44 153 103Liver 44 41 13 12Pancreas 108 103 8 8Pancreas 108 103 8 8Stomach 81 50 33 30Melanoma 145 27 1 8 1Melanoma 145 27 1.8 1Testis 21 1 3 1
Showing cases per 1 million persons calculated on the basis of current consensus:4545
Showing cases per 1 million persons calculated on the basis of current consensus: GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence
Worldwide, Version 1.0. IARC Cancer Base No. 5, Lyon, IARC Press, 2001.
Comparison of Cancer Incidence ‐2U S [curcumin non users] vs India [curcumin users]U.S [curcumin non‐users] vs. India [curcumin users]
Cancer US IndiaCancer US IndiaCases Deaths Cases Deaths
Bladder 202 43 15 11Bladder 202 43 15 11Kidney 115 44 6 4Brain Nervous Systems 65 47 19 14Brain, Nervous Systems 65 47 19 14Thyroid 55 5 12 3Endometrial Cancer 163 41 132 72Endometrial Cancer 163 41 132 72Ovary 76 50 20 12Multiple Myelome 50 40 6 5Multiple Myelome 50 40 6 5Leukemia 100 70 19 17Non‐Hodgkin’s lymphoma 180 90 17 15Non Hodgkin s lymphoma 180 90 17 15Hodgkin’s disease 20 5 7 4
Showing cases per 1 million persons calculated on the basis of current consensus:4646
Showing cases per 1 million persons calculated on the basis of current consensus: Endometrial cancers include Cervix, Uteri and Corpus uteri
GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0. IARC Cancer Base No. 5, Lyon, IARC Press, 2001.
Curcumin C3 Complex® ‐ Researchp
Diabetic Nephropathy Lichen planusDiabetic Nephropathy Lichen planus
Melanoma Cystic fibrosis
Colorectal cancer Multiple myeloma
Pancreatic cancer Oral cancer
COPD [ Lung inflammation ] Rheumatoid arthritis
Alzheimer’s Disease Head and Neck CancerAlzheimer s Disease Head and Neck Cancer
474747Sabinsa Corporation
Curcumin Bioavailability enhanced by Bioperine®
0.18
0.2
Curcumin + Bioperine
Curcumin
0.14
0.16
0.18
(g/m
l)
0 08
0.1
0.12
DoseC ien
trat
ion
0.04
0.06
0.08 Curcumin 2000 mgBioperine 20 mg
um c
once
0
0.02
0 25 0 5 0 75 1 2 3 4 5
Ser
0.25 0.5 0.75 1 2 3 4 5
Serum concentration of curcumin in healthy volunteers (n=8) after 4848
yadministration of curcumin with and without Bioperine
Curcumin BioavailabilityCurcumin Bioavailability
Sabinsa Corporation is currently working with a US b d h i t d Ph ti l tbased, research oriented Pharmaceutical company to effect studies with Curcumin in the form of nanosomes and liposomes in patients with various forms of cancerand liposomes in patients with various forms of cancer, particularly pancreatic cancer.
Nano‐liposomes can act as both encapsulation and delivery systems with new and exciting applications, particularly in the pioneering of anti‐aging research.
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