spicelecture

Add spice to your life

Bharat B. Aggarwal, Ph.D.

Professor of Medicine & BiochemistryChief, Cytokine Research Section

University of Texas M.D. Anderson Cancer Center

This presentation is for information only. Arya samaj and Dr. Aggarwal are not liable for any damages that may result from use of this information.

Bharat B. Aggarwal([email protected])

Ph.D. Biochemistry: 1973-77University of California, Berkeley

Postdoctoral Fellow: 1977-80University of California, San Francisco

Senior Scientist & Project Leader: 1980-89Genentech Inc., S. San Francisco

Professor of Medicine and Biochemistry and Chief, Cytokine Research Section: 1989-presentThe University of Texas, MD Anderson Cancer Center

Professor of Biochemistry (Adjunct): 1992-presentTexas A&M University (IBT), Houston

Published `350 original papers, seven books and 35 patents

Ancient spice route

Traditional Knowledge(Ayurvedic medicine)

Golden Triangle

Modern Knowledge(Allopathic medicine)

Modern technology

FDA Study Estimates Vioxx Linked to 27,000 Heart Attacks

October 6, 2004: 4:43 a.m. ESTWASHINGTON -- A study led by a Food and Drug Administration safety official projects that the widespread use of Vioxx may have led to more than 27,000 heart attacks and sudden cardiac deaths before the drug's abrupt withdrawal last week by Merck & Co. (MRK), Wednesday's Wall Street Journal reported.

The number is in comparison to how many similar incidents would have occuoccurred had the same patients been taking Celebrex, the Pfizer Inc. drug that competed with Merck's blockbuster arthritis treatment. The analysis specifically found that from Vioxx's approval in 1999, through 2003, an estimated 27,785 heart attacks and sudden cardiac deaths "would have been avoided" hadCelebrex been used instead of Vioxx.

J&J warns on lymphoma drug riskBy Val Brickates Kennedy, CBS.MarketWatch.comLast Update: 5:06 PM ET Oct. 8, 2004

BOSTON (CBS.MW) - Drugmaker Johnson & Johnson will send out a letter on Oct. 12 warning physicians that users of Remicade face an increased risk of developing the deadly cancer lymphoma.

According to a spokesman at Johnson & Johnson, the company received clearance from the Food and Drug Administration on Thursday night on the language of the letter.

The letter, which states that Remicade users are six times more likely to develop lymphoma, will be sent out to health professionals on Tuesday.Remicade, which is manufactured by Johnson & Johnson's biotechnology unit Centocor, already carries a warning that it can cause serious blood and neurological disorders.The drug, which is based on a monoclonal antibody, is used to treat such autoimmune disorders as Crohn's disease and rheumatoid arthritis.

Cell signaling network

Hypothesis!When under control, fire is good for us. However,

when out of control (dysregulated) fire can

burn everything!

Inflammation plays a major in development of most diseases

DysregulatedInflammation

Diabetes II

Pulmonarydiseases

CancerCardiovascular

diseases

Alzheimer

Autoimmunediseases

Arthritis

Neurologicaldiseases

TIME Feb. 23, 2004

The surprising link between Inflammation and Heart Attacks, Cancer, Alzheimer’s and other diseases

TIME Feb. 23, 2004

NF-κB activation is a major mediator of inflammation in most diseases & inhibition of NF-κB activation can suppresses inflammation

Hypothesis!

Chronic obstructive pulmonary diseases

Helicobacter pylori-associated gastritis

Viral infections

Sleep apnoea

Sepsis

AIDSArthritis

Cancer

HeadacheDiabetes

type 1 and II

Gut disease

Asthma

Neuropathological disease

Lupus

Aging

Skin disease

Renal disease

Heart failure

Ischemia/Reperfusion

Cardiac hypertrophy

AtherosclerosisMultiple sclerosis

Muscular dystrophy

Bone resorptionAlzheimer’s disease

Incontinentia pigmentiEctodermal dysplasia

Systematic inflammatory response syndrome

Crohn’s disease

Inflammation

Inflammation has been linked to several diseases

B cell lymphoma

Hodgkin’s disease

T cell lymphoma

Adult T cell leukemia

Acute lymphoblasticleukemia

Breast cancer

Liver cancer

Thyroid cancer

Prostatecancer

Melanoma

Pancreatic cancer

Head and neck SCCColon cancer

Multiple myeloma

Ovarian cancer

Bladder cancerLung cancer

NF-κB

Acute Myelogenous

leukemia

Cervical cancer

Nasopharyngeal carcinoma

Mantle cell lymphoma

Non-Hodgkin’s lymphoma

Viral cancers

Tobacco-linked cancers

UV light

CarcinogensCarcinogens

Esophageal cancer

Pharyngeal cancer

Renalcarcinoma

Laryngeal cancer

Cancers linked to constitutive activation of NF-κB

Working Model for Cigarette Smoke-Induced Damage

Cigarette smoke

Cardiovascular diseases:Restenosis,

AtherosclerosisMyocardial infarction

Chronic obstructive pulmonary diseases

(COPD):Chronic bronchitis &

Emphysema

Tumorigenesis:Lung, larynx, oral cavity,

pharynx, esophagus, pancreas, kidney and bladder

Rheumatoid arthritis

NF-κB

Total Deaths Due to Cancer in the USA*

Cancer 1971 2001Lung 53,000 90,000Colorectal 22,000 28,000Prostate 17,000 32,000Pancreas 10,000 14,000CML 4,500

Cancer 1971 2001Lung 11,000 67,000Colorectal 24,000 29,000Breast 31,000 ---Pancreas ---- ---

Men

Women

* War on Cancer (1976)

Cancer United States India

Prostate (Men) 61.8 6.9Breast (Women) 89.2 24.6Colon/rectum (Men) 46.3 6.4

(Women) 33.2 5.1Stomach (Men) 8.0 7.3

(Women) 3.5 4.3Lung (Men) 64.3 14.0

(Women) 29.9 3.0Oesophagus (Men) 4.0 11.4

(Women) 1.3 8.4

Source: Food, Nutrition and the Prevention of Cancer: a global perspectives by American Institute for Cancer Research, 1997

Comparison of cancers incidence between USA and India

(Rates per 100,000)

Comparison of Cancer IncidenceUSA India Japan

Cases Deaths Cases Deaths Cases DeathsOral cavity 50 11 102 60 29 12Nasopharynx 4 2 4 3 3 2Other Pharynx 19 9 57 42 10 7Oesophagus 31 31 63 59 58 43Stomach 56 34 43 39 489 225Colon/Rectum 356 139 40 26 342 143Liver 30 31 17 16 186 146Pancreas 72 68 11 11 76 71Larynx 33 11 35 22 17 5Lung 463 402 55 51 262 214Melanoma of skin 113 21 3 1 3 2Breast 914 212 191 99 314 77Cervix uteri 78 33 307 174 111 30Corpus uteri 155 20 17 5 45 13Ovary etc. 106 62 49 29 66 37Prostate 1043 179 46 28 111 55Testis 40 2 6 3 13 2Bladder 144 28 20 16 56 17Kidney etc. 86 31 8 6 42 19Brain, nervous system 54 37 21 16 24 9Thyroid 46 3 14 4 31 5Non-Hodgkin lymphoma 135 59 24 19 58 30Hodgkin's disease 22 4 8 4 3 1Multiple myeloma 35 26 8 6 16 12Leukemia 80 54 26 20 48 34All sites but skin 3223 1391 1017 688 2230 1213

Showing cases were after standardized with world standard population, called World Standardized incidence or mortality rate. It is also expressed per million. J. Ferlay, etal.GLOBOCAN 2000.URL: http://www-dep.iarc.fr/globocan/globocan.htm

Cancer

Drug-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. (Benowitz S, The Scientist 10, 1996, 1-7).

Approximately 25% of the drug prescription in the USA are compounds derived from plants and were discovered

through scientific investigation of folklore claims (Reynold T, J. Natl. Cancer Inst. 183, 1991, 594-596).

Examples:Pacific yew Taxol Rosy periwinkle Vinblastin and vincristineFoxglove DigitalisMeadowsweet Aspirin

Why natural products are goodSource of anticancer drugs?

Almost 74% (48/65) of all drugs approved either were natural products, were based thereon, or mimicked them

in one form or another (1981-2002)

Newman DJ, Cragg GM, and Snader KM., J. Nat. Prod., 2003, 66, 1022-1037.

Hippocrates proclaimed~2500 years ago

“Let food be thy medicine

and medicine be thy food”

“You are what you eat”

More Americans using alternative therapiesJune 1st, 2004

Development of therapeutics: opportunities within complementary and alternative medicine.

Engel LW, Straus SE. , Nat Rev Drug Discov. 2002 Mar;1(3):229-37.

Whereas other components of the NIH support the discovery and subsequent development of novel chemical entities into drugs, the National Center for Complementary and Alternative Medicine (NCCAM) studies complex natural products that are marketed as dietary supplements.

Regulatory framework for dietary supplements and drugs, outlines the challenges of evaluating dietary supplements for safety and clinical effectiveness, and describes the evolving drug model for botanicals.

Ayurveda (Sushruta Samhita)Ayurveda means “science of long life”.

This is an ancient medical system primarily practiced in India for over 6000 years.

Ayurveda is a part of life style and philosophy of Indians.

It emphasizes body, mind and spirit in disease prevention and treatment

It believes disease is caused by the imbalance of “tridoshas”(biomaterials), called vatta, pitta and kapha

Vatta controls all movementsPitta controls biotransformation (metabolism)Kapha controls cohesion and functions through body fluids

Together they control and conduct all functions of the body.

Ayuvedic medicine

Among the first drugs for the treatment of high blood pressure was

resperine from the herbRauwolfa serpentina.

Ayurveda (How to treat cancer?)

Sushruta recommends complete surgical removal of the malignant growths.

Incomplete removal is considered a conduit for recurrence.

Other treatments for cancer constitute: Therapeutic diet, Herbs, Detoxification, Breathing exercisesMassage

Adjuvant treatments for cancer therapy involves the usage ofRasayanas, a group of herbal drug preparations

AyurvedaThese rasayanas are potent protective agents against chemotherapeutic agents and radiation in pts with cancer undergoing chemotherapy and/or radiation therapy.

Chyavanprash is one type of rasayana prescribed for immune deficiency and helps body to fight the disease and protect from chemo/radiation therapy.

Chyavanprash was first described for its healing properties 2000 B.C.

Chyavanprash has prophylactic, curative and restorative functions.

Chyavanprash protects from age-associated degenerative changes.

AyurvedaThe primary ingredient of this formula is Embelica officinalis.

Several formulations of Chyavanprash exists:

Bhaishajya RatnavaliSharangadhara-SamhitaCharaka SamhitaAyurvedic formulary

Chyavanprash has 45 ingredients which falls in five categories:

1. Pradhana Dravya (primary ingredient)……EO (Amla)2. Samsadhana Dravya (blend of herbs)3. Yamaka dravya (lipids)4. Prakshep Dravya (flavoring or seasoning agents)5. Samvahaka dravya (perserving agent)

AyurvedaModern studies have shown that Chyavanprash has a potent free-radical scavening effects, prevents carcinogenesis and mutagenesis, and boosts the immune system in pts undergoing chemotherapy.

EO, also called Amla, has been shown to exhibit antoxidant,hepatoprotective, antibacterial, antiinflammatory,hypocholerolemic, adaptogenic, immunomodulatory,cytoprotective and anti-tumor activities.

These activities are assigned to emlicanin A. emblicanin B,punigluconin, pedunculagin.

Clinical trials with Breast cancer and H&N cancer patients, has shown that Chyavanprash can protect patients from toxicity induced by radiation treatment

Spices can block NF-κB activation

Chemical Composition of Most Common SpicesSpice Botanical name* Part of Plant Major ConstituentsTumeric Curcuma longa rhizome Essentil oils 5%: tumerone (58%),

borneol (6.5%), cineole (1%),

a-phellandrene (1%), curcumin (0.6%),

zingerone, zingiberene (25%)

Pepper (red) Capsicum frutescens fruit Pigments: carotene, zeaxnthin,

cryptoxanthin; oleoresin (1.5%);

capsaicin

Cloves Syzgium aromaticum buds Essential oils 17%: eugenol (93%),

caryophyllin, vanillin, Eugenin,

(Caryophyllus aromaticus, methylamylketone

Eugenia caryophyllata)

Coriander Coriandrum sativum seeds Essential oils 1%: (+)-linalool (60-70%), a-pinene, b-pinene, a-terpinene, b-terpinene, geraniol, borneol, decylaldehyde, dipentene, cymene

Cumin Cuminum cyminum seeds Essential oil 4.5%: cuminaldehyde (40-65%),thymol, cymol, cymene

Chemical Composition of Most Common Spices

Spice Botanical name* Part of Plant Major ConstituentsCinnamon Cinnamomum zeylanicum bark Essential oils 1.5-2.5%: cinnamaldehyde (65-

75%), (-)-linalool, furfural, methylamylketone, nonylaldehyde, benzaldehyde, hydrocinnamaldehyde, cuminaldehyde, eugenol, caryophyllene, (-)-phellandrene, p-cymene, a-pinene

Allspice Pimenta dioica berry Volatile oil 4.5%; eugenol (80%), O-methyl (P. officinalis) eugenol, cineole, phellandrene,

caryophyllene%)

Fennel Foeniculum vulgare seeds Essential oils 6%: anethole (50-60%), (+)-fenchone (15-20%), a-pinene, camphne,

(+)-a- phellandrene, dipentene, p- hydroxy-phenylacetone, estragole, anisaldehyde, anisicacid, 1,3-dimethylbutadiene

Anise Pimpinella anisum seeds Fixed oil 8-20%; essential oil 1.5%; anethole (90-96%), estragole (2%), p- methoxyphenylacetone

Star anise Illicium verum seeds Essential oils 8-9%: anethole (88%), limonine (5%), estragole, safrole, p-methoxy-phenylacetone

Spice Botanical name* Part of Plant Major ConstituentsGinger Zingiber officinale rhizome Essential oils 1-2.5%: zingerone, shogaol,

gingerol, cineole, borneol, geraniol, linalool, farnesene, citral, zingiberene, zingiberol, camphene, phellandrene, methyl heptanone

Basil Ocimum basilicum Essential oil: (+)-linalool (40%), estragole (25%), eugenol, cineole, geraniol

Cardamon Elettaria cardomonum seeds Fixed oils 1-2%: fatty acid glycerides;essential oils 2-10%: cineole (25-40%), methylheptanone, terpenene, a-terpinyl acetate (28-34%), b-terpineol, borneol, nerylacetate, geraniol, nerolidol, a-pinene, sabinene, mycrene, limonene, p-cymene

Capers Capparis sppinosa seeds Fixed oil 15%: fatty acids; essential oil 7.5%: Caraway Carum carvi (+)-carvone (60%), carvol, (+)-limonene,

carveol, diacetyl, furfural

Curry Leaves Murraya koenigii leaves Essential oils 4.0%: carvone (60%),

Dill Anethum graveolens dihydrocarvone, (+)-limonene, aphellandrene, a-pinene, dipentene


Spice Botanical name* Part of Plant Major ConstituentsFenugreek Trigonella foenumgraecumseeds Fixed oils 7%: trigonelline, choline Essential

Garlic Allium sataivum bulb oils 0.2%: diallyldisulfide (60%), diallyltrisulfide (20%), allylpropyldisulfide (6%), alliin, allicin

Lemon Grass Andropogon nardus grass Essential oils 0.3-0.55%:citral(70-85%),(A. citratus);Cymbopogon geraniolcitratus (C. flexuosus)

Licorice Glycyrrhiza glabra rhizome Water extract: glycyrrhizin 12-20% Essential oils

Mace Myristica fragrans aril 1115%:monoterpenes(88%), monoterpenols (55%)

Mint (black) Mentha vulgaris (M. Piperita) Essential oils 1%: a-pinene, b-pinene, limonene,

Mint (white) M. officinalis cineole, ethylamylcarbinol, (-)-menthol, menthone, menthylacetate, piperitone

Mustard (white)Brassica alba (B. hirta, seeds Fixed oils 30-35%; sinalbinB. Juncea, Sinapsis alba)

Mustard (black)B. Nigra (S. nigra) seeds Sinigrin


Spice Botanical name* Part of Plant Major ConstituentsNutmeg Myristica fragens seeds Fixed oils 24-30%; essential oils 16%; elemicin

(2%), eugenol, isoeugenol, o-methyleugenol, safrole (0-6%), myristic acid, a-pinene, sabinene, (+)-camphene (60-80%), dipentene (8%), geranioil,(+)-borneol,(-)-terpeneol, myristicin(4%)

Oregano Oreganum vulgare Essential oils: thymol 50%, a-pinene 7-8%, cineole, linalyl acetate,linalool, dipentane, p-cymene, b-cymene, b-cryophyllene

Pepper (black) Piper nigrum unripe fruit Essential oils 1.5%: monoterpenes (70-80%)

Pepper (white) ripe fruit Sesquiterpenes (20-30%), chavicine; oleoresin: piperine, piperidine

Rosemary Rosmarinus officinalis twigs Essential oils 2%: borneol (16-20%), cineole (27-30%), camphor (10%), bornyl acetate (2-7%), a-pinene camphene, terpinol, verbenone

Saffron Crocus sativus stigmas Essential oils 1%: 2,2,6-trimethyl-4,6-cyclohexadienal, crocin, picrocrocin, crocetin

Sesame Sesamum indicum seeds Fixed oils: 45-65%

Spearmint Mentha spicata Essential oils 0.6%: (-)-carvone (56%), dihydrocuminyl esters, dihydrocarveyl acetate


CinnamonIntake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes

The inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.

Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling

Accelerates wound healing

Cinnamon & diabetesCinnamon improves glucose and lipids of people with type 2 diabetes.

The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the

inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.

Khan A, ……Anderson RA. Diabetes Care. 2003 Dec;26(12):3215-8.

Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats.

Qin B, …….Sato Y. Diabetes Res Clin Pract. 2003 Dec;62(3):139-48.

Regulation of PTP-1 and insulin receptor kinase by fractions fromcinnamon: implications for cinnamon regulation of insulin signalling.

Imparl-Radosevich J, ……….. Graves DJ. Horm Res. 1998;50:177-82.

Cinnamon extracts' inhibitory effect on Helicobacter pylori.J Tabak M,….Neeman I. Ethnopharmacol. 1999;67(3):269-77.

CorrianderApogenin

Apogenin is a potent antioxidant

Exhibits insulin-releasing and insulin-like activity

Exhibits hypolipidemic effect

Exhibits hypotensive effects

Coriander (Coriandrum sativum)

Insulin-releasing and insulin-like activityof the traditional anti-diabetic plant

coriander. Gray AM, Flatt PR. Br J Nutr. 1999 Mar;81(3):203-9.

Hypolipidemic effect of coriander seeds mechanism of action.

Chithra V, Leelamma S. Plant Foods Hum Nutr. 1997;51(2):167-72.

Curry leavesCarbazole alkaloids

Potent antioxidant

Hypoglycemic

Antifungal

Fennel

OCH3

HC CHCH 3

Anethole[1-Methoxy-4-(1-propenyl benzene)

Anethole suppresses NF-κB activation

Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-kappaB, AP-1, JNK, MAPKK and apoptosis.

Chainy GB, Manna SK, Chaturvedi MM, Aggarwal BB.Oncogene. 2000;19(25):2943-50.

FennelAnethol

Potent antioxidant

Hepatoprotective

Antifungal

Antibacterial

Fenugreek4-hydroxyisoleucine, Diosgenin

Fenugreek has a long history of medical uses in Ayurvedic and Chinese medicine.

Tradionally used for labor induction, and for aiding digestion,

Preliminary animal and human trials suggest possible hypoglycemic andantihyperlipidemic properties of oral fenugreek seed powder.

For diabetes, fenugreek reduces insulin resistance through activation of the early steps of insulin signaling in peripheral tissues and in liver.

For hyperthyroidism, trigonella (200 mg/kg) was found to lower the serum concentrations of T3 and T4

Supplementation of fenugreek seeds in the diet inhibits colon carcinogenesis, by modulating the activities of beta-glucuronidase and mucinase.

Stimulates immune functions

Antiulcer potential

Nematicidal activity

PiperineScientific evidence on the role of Ayurvedic

herbals on bioavailability of drugs.Atal CK, Zutshi U, Rao PG. J Ethnopharmacol. 1981;4:229-32.

Experiments were conducted to evaluate the scientific basis of the use of the trikatu group of acrids (long pepper, black

pepper and ginger) in the large number of prescriptions inAyurveda.

Impairment of UDP-glucose dehydrogenase andglucuronidation activities in liver and small

intestine of rat and guinea pig in vitro by piperineReen RK, Jamwal DS, Taneja SC, Koul JL, Dubey RK, Wiebel FJ, Singh J..

Biochem Pharmacol. 1993;46:229-38.

Black pepperPiperine

Trikatu group (long pepper, black pepper and ginger) is used in the large number of prescriptions in Ayurveda

Enhances drug bioavailability

Inhibits glucuronidation activity

Hepatoprotective

Inhibits human P-glycoprotein and CYP3A4

Piperine inhibits gastric emptying.

Singh et al, Journal of Immunology, 157, 1996, 4412-20

Capsaicin

Red chilli-

+ +

Capsacin suppresses NF-κB activation by inhibiting IκBα degradation

O

HO

N�H

O

Vanillyl Acyl amide Alkyl

OH

OCH 3

HC CHCH 3

OH

OCH 3

H2C

Isoeugenol

CH

CH2

Eugenol

[2-Methoxy-4 propenylphenol]

[2-Methoxy-4-(2-propenyl) phenol]

Eugenol suppresses NF-κB activation

Cloves

Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-kappaB, AP-1, JNK, MAPKK and apoptosis.

Chainy GB, Manna SK, Chaturvedi MM, Aggarwal BB.Oncogene. 2000;19(25):2943-50.

ClovesEugenol

Antibacterial (inc. Helocobacter pylori)

Antiviral (Herpes, CMV,HSV)

Antimutagenic

Inhibits growth of oral pathogens

Inhibits platelet aggregation

GingerGingerol

Treatment of nausea and vomiting

Anti-diabetic

Pregnancy-induced nausea

Reduces hyperglycemia

Reduces motion sickness

TaminrindusGingerol

Antiinflammatory

Anti-diabetic

Antioxidant

Curcumin

Time, 2004

Withania somniferaAshwagandha

Indian ginseng used to maintain positive state of mental and physical health.

Ashwagandha(Withania sominifera)

The roots of Withania somnifera (WS) are used extensively in Ayurveda, and is categorized as a rasayana, which are used to promote physical and mental health, to provide defense against disease and adverse environmental factors and to arrest the aging process.

WS has been used to stabilize mood in patients with behavioral disturbances.

WSG exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swim-induced 'behavioural despair' and 'learned helplessness' tests.

The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression in Ayurveda.

Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study.Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S.

Phytomedicine. 2000;7:463-9.

Withania (Ashwagandha)Withania somnifera root extract prevents DMBA-inducedsquamous cell carcinoma of skin in Swiss albino mice.

Prakash J, Gupta SK, Dinda AK. Nutr Cancer. 2002;42:91-7.

Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction.Mohanty I, ….. Gupta SK. Basic Clin Pharmacol Toxicol. 2004;94:184-90.

Immunoprotection by botanical drugs in cancer chemotherapy.

-Withania somnifera (Linn Dunal) (Solanaceae),-Tinospora cordifolia (Miers) (Menispermaceae), -Asparagus racemosus (Willd.) (Liliaceae), Immunopharmacological activities in cyclophosphamide (CP)-treated mouse ascitic sarcoma; resulted in protection towards CP-induced myelo- and immunoprotection as evident by significant increase in white cell counts and hemagglutinating and hemolytic antibody titers.

Diwanay S, Chitre D, Patwardhan B. J Ethnopharmacol. 2004 Jan;90(1):49-55.

TriphalaTerminalia chebula, Emblica officinalis, Terminalia bellerica

Triphala is one of the rasayana that promotes, health, and longevity.

It is used to treat anemia, jaundice, constipation, asthma, fever and chronic ulcers.

Triphala has radioprotective effects in mice (Jagetia GC, 2002).

Emblica officinalis has anticlastogenic activity (Talukder G etal, 1997)

Emblica officinalis has antitumor activity (Jose JK etal, 2001)

Terminalia chebula has antiproliferative activity (Saleem A etal, 2002)

Source: Ajanta Pharmaceuticals, Mumbai

Guggulsterone is used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis.

Commiphora mukul (guugul)

O

O

HH3C

A natural product that lowers cholesterol as an antagonist ligand for FXR.Urizar NL, et al Science. 2002;296:1703-6.

Guggulsterone inhibits NF-κB andIκBα kinase activation, suppresses expression of antiapoptotic gene

products and enhances apoptosis

Shishir Shishodia, and Bharat B. Aggarwal

Journal of Biological Chemistry 2004 Aug 17 [Epub ahead of print]

Boerhavia diffusa(punarnava; Family Nyctaginaceae)

Creeping weed

Roots are used for the treatment of dyspepsia, jaundice, enlargement of spleen, abdominal pain (Kirtikar & Basu, 1956)

Used as anti-stress agent (Chopra etal, 1996)

Liridendrin derived from it has calcium channel antagonist activity (Lami etal, 1991)

Used for analgesic and antiinflammatory properties (Hiruma-Lima etal, 2000)

Protects mice against E. Coli induced peritonitis (Mungantiwar,1997, 1999)

Has antiproliferative and immunomodulatory activites (Mehrotra etal, 2001, 2002)

Fruits & VegetablesOur review of 206 human epidemiologic studies and 22 animal studies suggests the existence of an inverse relationship between consumption of vegetables and fruits and risk for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon .

The types of vegetables or fruits that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes.

Substances present in vegetables and fruit that may help protect against cancer usually include dithiolthiones, isothiocyanates, indole-3-carbinol (I3C), allium compounds, isoflavones, protease inhibitors, saponins,phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber.

Noncancer-related effects of increased vegetable and fruit consumption include benefits against cardiovascular disease, diabetes, stroke, obesity,diverticulosis, and cataracts.

FruitsBlackberriesBlueberriesBlack currantsDried plumsElderberriesPurple figsPurple grapesPlumsRaisinsVegetablesPurple asparagusPurple carrotsEgg plantPurple peppersPurple potatoesBlack salsify

FruitsAvacadosGreen applesGreen grapesHoneydewKiwifruitLimesGreen pearsVegetablesArtichokesAsparagusBroccoliBrussels sproutsGreen beansGreen cabbageCeleryCucumbersLettuceOkra and PeasSpinach Watercress

FruitsBananasDatesWhite nectarinesWhite peachesBrown pearsVegetablesCauliflowerGarlicGingerKohlrabiMushroomsOnionsPotatoesShallotaTurnipsWhite corn

FruitsYellow applesApricotsCantaloupeGooseberriesYellow figsGrapefruitGolden kiwifruitLemonsMangoesNectarinesOrangesPapayasPeachesPineapple Tangarines VegetablesCarrots and BeetsYellow peppersPumpkinSweet ccornYellow tomatoes

FruitsApplesBlood orangesCherriesCranberriesRed grapesRed pearsPomegranatesRaspberriesStrawberriesWatermelon VegetablesBeetsRed cabbageRed peppersRadishesRed onionsRed potatoesRhubarbTomatoes

Potential sources of NF-κB blockersCancerUrinary tractMemory and Aging

CancerHeartCholesterol

CancerVisionBones

CancerHeart, visionImmune system

CancerHeart, memoryUrinary tract

LycopeneAnthocyanins

Vitamin C, CaroteinidsBioflavonoids

AllicinLuteinIndoles

AnthocyaninsPhenolics

Surh YJ, Nature Rev Cancer. 2003 Oct;3(10):768-80

Vegetables can block NF-κB activation

Spices, fruits and vegetablescan block NF-κB activation

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Kohlrabi

Collard greens

Arugula

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Rutabaga/Turnips

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Radishes



Watercress



Kale



Mustard greens



Chinese cabbage



Brussels sprouts



Broccoli

Cauliflower

Daikon

Cabbage



QuickTime™ and aFF (Uncompressed) decompressor


Pok choy

NH

CH2OH

Indole-3-carbinol

Cruciferous vegetables

Suppress the tumorigenesis of the colon , lung , breast, cervix and liver .

Effective clinically in treating precancerous lesions of the cervix and laryngeal papillomas.

Alters the immune function, inhibit cigarette smoke-induced DNA-adduct formation , and reverse multidrug resistance in vivo.

Indole 3-carbinol

From Takada and Aggarwal, submitted)

Indole-3-carbinol (I3C) is found in Brassica sp.vegetables such as cabbage, cauliflower, and brussels spouts.

It exhibits anticarcinogenic, antimetastatic, andantiproliferative activities.

Indole-3-carbinol Abolishes Carcinogen-Induced NF-κB and IκBα Kinase Activation Causing Suppression of NF-κB-RegulatedAntiapoptotic and Metastatic Gene Expression and Upregulation of Apoptosis

Lupeol

Mango

Olive

Fig

LupeolLupeol, a triterpene, is the principal constituent of common fruit plants such as olive, mango, fig and medicinal herbs that have been used to treat skin aliments.

Lupeol has been reported to possess a wide range of medicinal properties that include strong antioxidant, antimutagenic, anti-inflammatory and antiarthritic effects.

Resveratrol

HO

HO

OH

Polygonum cuspidatumKo-jo-Kon (Japanese)

Arachis hypogeaPeanut

Vitis viniferaGrapes

Morus rubraMulberry

Pinus sylvestrisScots pine

Artocarpus sp.Jackfruit

Vaccinum sp.Cranberry

Cassia sp.Legumes

Eucalyptus Bauhinea sp.

Rheum rhaponticumRheum

Gnetum montanum Veratrum sp.Corn lily

Vaccinum sp.Blueberry

Picea sp.Spruce

Veratrum grandiflorumWhite hellebore

Sources of resveratrol

DrakshasvaAn Ayurvedic remedy, also called Manakka

Cardiotonic

Antiinflammatory

Antioxidant

Anticancer-Chemopreventive

Piceatannol Resveratrol

Stilbene trans-3, 4', 5-trihydroxystilbene

Resveratrol suppresses NF-κB activation without inhibiting IκBα degradation

Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen

intermediates and lipid peroxidationManna SK, Mukhopadhyay A, Aggarwal BB.

Journal of Immunology, 164, 2000, 6509-6519

Piceatannol inhibits TNF-induced NF-kappaB activation and NF-kappaB-mediated gene expression through suppression of IkappaBalpha kinase and p65

phosphorylation.Ashikawa K, Majumdar S, Banerjee S, Bharti AC, Shishodia S, Aggarwal BB.

Journal of Immunology 2002;169:6490-7.

Sources of Caffeic Acid Phenethyl Ester

Poplar flower Beech tree Chestnut tree

Propolis of honey bee

HO

HO

O

O

Caffeic Acid Phenethyl Ester

Sources of Sanguinarine

Sanguinaria canadensis Poppy

Fumaria sp.Root of Sanguinaria canadensis

Berberine

Sanguinarin suppresses NF-κB activation by inhibiting IκBα degradation

--+

O

O

+NO

OCH3

O

O

+NOCH3

OCH3CH3

Cl-N

OO

OCH3OCH3+

Chelerythrine chlorideSanguinarine

Sanguinarine (pseudochelerythrine) is a potent inhibitor of NF-kappaB activation, IkappaBalpha phosphorylation, and degradation.Chaturvedi MM, Kumar A, Darnay BG, Chainy GB, Agarwal S, Aggarwal BB.

Journal of Biological Chemistry. 1997; 272:30129-34.

Emodin suppresses NF-κB activation through suppression of IκBα degradation

O

O

CH 3

OHOH

HO

Emodin(3-methyl-1,6,8-trihydroxyanthraquinone)

AloeEmodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-

kappaB activation, IkappaB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells.

Kumar A, Dhawan S, Aggarwal BB. Oncogene. 1998;1:913-8.

HO

OH

H

OH

O

O

H

CH2OH

OCH3

OH

H

H

Silymarin

O

O

Manna et al Journal of Immunology, 163, 1999, 6800-6809

Silymarin suppresses NF-κB activation by inhibiting IκBα degradation

Artichok

Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis.

Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. J Immunol. 1999 Dec 15;163(12):6800-9.

Sources of Genistein

Soy plant Soy pod Soy beans

O

OHOH

HO

O

SoybeanProtein tyrosine kinase inhibitors

block tumor necrosis factor-induced activation of nuclear factor-kappaB,

degradation of IkappaBalpha, nuclear translocation of p65, and

subsequent gene expression.

Natarajan K, Manna SK, Chaturvedi MM, Aggarwal BB.

Arch Biochem Biophys. 1998;352:59-70.

Nerium oleander

OH

H3C

O

O CH 3

OH

H

H3C

OO

H

HO

H3CO

O

Oleandrin

Oleandrin suppresses activation of nuclear transcription factor-

kappaB, activator protein-1, and c-Jun NH2-terminal kinase.

Manna SK, Sah NK, Newman RA, Cisneros A, Aggarwal BB.

Cancer Research 2000;60:3838-47.

BearberryCranberry

Sources of ursolic acid

Rosemary Makino

Prunes

Apple

Holy basilPears CH3

CH3

H3C

HOH3C

CH3 CH3 H

CH3

COOH

Basil Tulsi(Ocimum sanctum)

In several ancient systems of medicine including Ayurveda, Greek, Roman, Siddha and Unani, Ocimum sanctum has vast number of therapeutic applications such as incardiopathy, haemopathy, leucoderma, asthma, bronchitis, catarrhal fever, otalgia,hepatopathy, vomiting, lumbago, hiccups, ophthalmia, gastropathy, genitourinary disorders, ringworm, verminosis and skin diseases etc. The present review incorporates the description of O. sanctum plant, its chemical constituents, and various pharmacological activities.Gupta SK, Prakash J, Srivastava S. Indian J Exp Biol. 2002 ;40:765-73.

Chemopreventive activity of Ocimum sanctum seed oil.The results of this study suggest that the potential chemopreventive activity of the oil is partly attributable to its antioxidant properties. The chemopreventive efficacy of 100 microl/kg seed oil was comparable to that of 80 mg/kg of vitamin E.4.Prakash J, Gupta SK. J Ethnopharmacol. 2000;72:29-3

Lens aldose reductase inhibiting potential of some indigenous plants.Cataract is the leading cause of blindness worldover. Diabetes is one of the major risk factors for cataractogenesis and aldose reductase (AR) has been reported to play an important role in sugar-induced cataract. OS possesses a significantanticataract activity in vitro and its anticataract potential could be related with its AR inhibitory effectHalder N, Joshi S, Gupta SK. J Ethnopharmacol. 2003;86:113-6.

Ursolic Acid Inhibits NF-κB Activation Induced by Carcinogenic Agents

Through Suppression of IκBα Kinase and p65 Phosphorylation:

Correlation with Downregulation of COX2, MMP-9 and CyclinD1

Shishodia S., Majumdar S., Banerjee S. and Aggarwal B. B.

Cancer Research 2003, 63, 4375-83

Zizyphus mauritiana

Sources of betulinic acid

Syzygium formosanumPlatanus acerifolia Tryphyllum peltaum

Zizyphus sp

Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis.

Pisha E,, et al. Nature Medicine 1995 Oct;1(10):1046-51

H

CH3CH3

HO

H3C CH3

H CH3

H

CH3

H2C

OH

Betulinic acid Suppresses Carcinogen-Induced NF-κB

Activation Though Inhibition of IκBα Kinase and p65

Phosphorylation

Takada Y. and Aggarwal B. B.

Journal of Immunology,2003, 171, 3278-86

Flavopiridol

Flavopiridol is a semisynthetic flavonoid closely related to a compound originally isolated from the

stem bark of Dysoxylum binectariferum (also calledrohitukine), a plant indigenous to India.

Flavopiridol has been found to inhibit cyclin-dependent kinases, induce apoptosis, suppress

inflammation, and modulate the immune response.

O

OH

HO

N

OH

CH 3

O

Cl

Flavopiridol inhibits NF-κB activation induced by various carcinogens and inflammatory

agents through inhibition of IκBαkinase and p65 phosphorylation

Takada Y, Aggarwal BB.

Journal of Biological Chemistry. 2004;279:4750-9.

Amoora rohitukaAmoora rohituka stem bark is one of the components of

a medicinal preparation used in the Indian Ayurvedicsystem of medicine for the treatment of human

malignancies.

Amooranin (AMR) is a triterpene acid isolated from the stem bark of a tropical tree grown wild in India.

Novel drug amooranin induces apoptosis throughcaspase activity in human breast carcinoma cell lines.

Rabi T, …. Escalon E. Breast Cancer Res Treat. 2003;80:321-30.

Amooranin overcomes multidrug resistance in human leukemia and colon carcinoma cell lines.

Ramachandran C, …. Escalon EA. Int J Cancer. 2003;105:784-9.

QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.

Alpina galanga

1’- Acetoxychavicol acetate

Rhizomes

AcO

12

3

45

6

1'2'

3'

Suppression of NF-κB and IκBαKinase Activation by 1'-

Acetoxychavicol Acetate Inhibits Invasion and Potentiates Apoptosis

Through Abrogation of NF-κB Regulated Gene Products

Haruyo Ichikawa, Yasunari Takada, Akira Murakami, Bharat B. Aggarwal

Submitted

QuickTime™ and aFF (Uncompressed) decompressorare needed to see this picture.



Medicinal Evodia Fruit Plant



Evodia rutaecarpa



Evodiamine

N

N

NH

O

H3C

N

Dried Evodia FruitEvodia Fruit



Wu-Zhu-Yu, Go-syu-y/u

Evodiamine Abolishes Carcinogen-Induced NF-κB and IκBα Kinase Activation Causing

Suppression of NF-κB-RegulatedAntiapoptotic, and Metastatic Gene

Expression Leading toUpregulation of Apoptosis

Takada Y, Kobayashi Y., & Aggarwal B. B.

(in preparation)

QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.

The dried rhizome of a herbaceous plant, turmeric is closely related to ginger. The spice is also sometimes called 'Indian saffron' thanks to its brilliant yellow color. Indian turmeric has been known to the world since ancient times. Several unique properties of Indian turmeric make it the ideal choice as a food flavor, an effective ingredient in medicines and cosmetics, and as a natural colorant.

Culinary U sesIn India it i s usedto tint many sweet dishes. Apart from its wide use in M oroccan cuisineto spice meat, particularly lamb, and vegetables, its principal place is in curri es and currypowders. It is used in many fi sh curries, possibly because it successfull y masks fishyodours. When used in curry powders, it is usuall y one of the main ingredients, providingthe associated yell ow colour.

Attr ibuted M edicinal PropertiesTurmeric is a mild digestive, being aromatic, a stim ulant and acarmi native. An ointmentbase on the spice is usedasan antiseptic in Malaysia. Turmeric water is an Asiancosmetic appli ed to impart a golden glow to the complexion. Curcumin has beenshownto be active against Staphlococcus aureus (pus-producing infections) and cancer.

Turmeric

Curcumin

Curcuma longa root Turmeric (spice)

Diferuloylmethane (dye) Traditional medicines & herbal remedies

UKON(Japanese Turmeric)

UKON-Tea UKON-Powder

UKON-PillUKON-Pill (portable)

UKON-Drink

UKON-Rice Topping

UKON-vinegar

Ryukyu Bio-Resource Development Co., LTD. OKINAWA, Japan

OH

O O

OCH3CH3O

HO

Diferuloylmethane; MW 368

Structure of Curcumin

Therapeutic potential of curcumin

CurcuminChemopreventive

Skin, liver, colon, stomach

Diabetes

Cardiovasuclar diseasesCholestrol, platelet aggregation, inhibition of smooth muscle cell

proliferation

Arthritis

Antiflammatory

Chemotheraputic

Antioxidant

Lung fibrosis

Nephrotoxicity

Cardiotoxicity Wound healing HIV replication

Cataract formation

Antiangiogenic

Multiple sclerosis

Alzheimer disease

Gall-stones formation

Curcumin

NF-κB ↓AP-1 ↓Egr-1 ↓

STAT1 ↓STAT3 ↓STAT5 ↓

EpRE ↓CBP ↓

β-catenin ↓

IKK ↓EGFR ↓HER2 ↓AKT ↓

JAK2 ↓TYK2 ↓

PKC ↓

Src ↓

PKA ↓JNK ↓

Cyclin D1 ↓ MMP9 ↓COX2 ↓5-LOX ↓ iNOS ↓ IL-12 ↓TNF ↓IL-6 ↓IL-8 ↓

FTPase ↓

Xanthine oxidase ↓Hemeoxygenase ↑uPA ↓GST ↑ GSH-pxICAM-1 ↓VCAM-1 ↓

ELAM-1 ↓TF ↓

Bcl-2 ↓ Bcl-xl ↓

P53 ↑AR/ARP ↓ MDR ↓

Gene expression

Protein kinases

Transcription factors

Others Enzymes

F3

PPARγ ↑

Nrf2 ↑

Molecular targets of curcumin

From Aggarwal B et al, Anticancer Research 23, 2003, 363-398

CurcuminCurcumin confers radiosensitizing

effect in prostate cancer cell line PC-3

Radiation upregulated TNF leading to an increase in NF-κB activity resulting in the induction of Bcl-2 protein.

Curcumin in combination with radiation inhibited TNF-mediated NF-κB activity resulting in bcl-2 protein

downregulation.

Chendil D, et al Oncogene 2004, 26:1599-607.

Overexpression ofOncogenes HER2 Growth factors

(e.g; EGF, PDGF, FGF)Growth factor receptorsSurvival factors

(e.g; Survivin,Bcl-2 and Bcl-xl) Cyclin D1Decoy receptor

Overexpression ofMatrix metalloproteasesCyclooxygenase-2Adhesion moleculesChemokine TNFTumor Suppressor genes

Proliferation InvasionTumor

MetastasisNormal

cellsTumor cells

TransformationTumorgrowth

Constitutive activation of transcription factors

AP-1& NF-κB

Different stages of cancer progression and its suppression by curcumin

curcumin

From Aggarwal B etal, Anticancer Research 23, 2003, 363-398

CurcuminDorai T, Gehani N, Katz A.

Therapeutic potential of curcumin in human prostate cancer-I.curcumin induces apoptosis in both androgen-dependent and

androgen-independent prostate cancer cells.Prostate Cancer Prostatic Dis. 2000;3:84-93.

Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III.Curcumin inhibits proliferation, induces apoptosis, and inhibits

angiogenesis of LNCaP prostate cancer cells in vivo.Prostate. 2001;47:293-303.

Dorai T, Gehani N, Katz A. Therapeutic potential of curcumin in human prostate cancer. II.

Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein.

Molecular Urology. 2000;4:1-6.

CurcuminNeuroprotective role of curcumin from curcuma longa on ethanol-

induced brain damage

Oral administration of curcumin to rats caused a significant reversal in lipid peroxidation, brain lipids and produced enhancement of glutathione in ethanol intoxicated rats

Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VPPhytother Res. 1999 Nov;13(7):571-4

CurcuminThe curry spice curcumin reduces

oxidative damage and amyloid pathology in an Alzheimer

transgenic mouse.

Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM.

J Neurosci. 2001;21:8370-7.

CurcuminPhenolic anti-inflammatory antioxidant

reversal of A beta-induced cognitive deficits and neuropathology

Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM.

Neurobiol Aging. 2001;22:993-1005

CurcuminProtective effects of curcumin against ischaemia/reperfusion

insult in rat forebrain.

Ghoneim AI, Abdel-Naim AB, Khalifa AE, El-Denshary ES.

Pharmacol Res. 2002;46:273-9.

Curcumin & RadiationRadioprotective action of curcumin extracted from Curcuma longa

LINN: inhibitory effect on formation of urinary 8-hydroxy-2'-deoxyguanosine, tumorigenesis, but not mortality, induced by γ-ray

irradiationInano H, Onoda M. Int J Radiat Oncol Biol Phys. 2002;53:735-43.

Prevention of radiation-induced mammary tumorsInano H, Onoda M. Int J Radiat Oncol Biol Phys. 2002;52:212-23

Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats

Inano H, Onoda M, Inafuku N, Kubota M, Kamada Y, Osawa T, Kobayashi H, Wakabayashi K..Carcinogenesis. 2000;21:1835-41.

Chemoprevention by curcumin during the promotion stage oftumorigenesis of mammary gland in rats irradiated with gamma-rays.

Inano H, Onoda M, Inafuku N, Kubota M, Kamada Y, Osawa T, Kobayashi H, Wakabayashi K. Carcinogenesis. 1999;20:1011-8.

Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity.

Thresiamma KC, George J, Kuttan R. J Exp Clin Cancer Res. 1998;17:431-4.

Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.

Cheng AL, et al Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.

Tested on 25 pts (13 men & 12 women) with a median age of 60 yrs (36-77)

Curcumin was administered orally 8000 mg/day

Patients No. Histological responseRecently resected bladder cancer; 2 1/2Oral leukoplakia, 7 2/7Intestinal metaplasia of the stomach; 6 1/6CIN 4 1/4Bowen’s disease 6 2/6

All pts (except 2) completed 3 months treatment regimen

Peak serum conc. of curcumin at 1-2 h after oral intake was 0.4-1.6 uM

Conclusion: Curcumin is not toxic to humans even at the high dose (8000 mg/day).

Egan ME, etal; Science. 2004;304:600-2.

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosistransmembrane conductance regulator (CFTR).

The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation.

Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely.

Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect.

These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells.

Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects

Curcumin & Skin DiseasesCurcumin-induced suppression of phosphorylase

kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and

immunohistochemical parametersMCY Heng, MK Song, J. Harker and MK Heng,

Br. J. Dermatology, 143, 2000, 937-949

Psoriasis, Actinic keratosis, Acne,Warts, Dermatitis, EczemaWound healing, Sunburn

Skin cancer

Treatment of psoriasiswith Psoria-Gold

After4 weeks

Before

R Knee L Knee L Leg L Elbow

12-05-2003

11-07-2003

Courtesy of Dr. Madeline Heng from UCLA

MCY Heng, MK Song, J. Harker and MK Heng, Br. J. Dermatology, 143, 2000, 937-949

Curcumin induced apoptosis in scleroderma lung

fibroblasts: role of PKCε

Tourkina E, Gooz P, Oates JC, Ludwicka-Bradley A, Silver RM, Hoffman S

Am J Respir Cell Mol Biol. 2004;31:28-35.

Curcumin and scleroderma

Topical Application of Curcumin

How to prevent cancer?Eliminate smoking

Exercise regularly

Eat a balanced diet and stay trim

Avoid sunburn

To detect early-stage cancer, undergo check ups:mammography; colonoscopy; prostate exam and PSA

Practice caloric restriction

Limit alcohol consumption

Keep positive attitude and stress-less life

Self-control & discipline is better than pills

Thank you!Gracias!

MercyShalom!Arigato!

Shei-shei!Gamsa hamnida!

Namaste!

spicelecture

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