TANNINS AND HUMAN HEALTH: Nutraceuticals effect of Tannin and its Monomers. MAYANK TANDON & DR. S.N. RAI Animal Nutrition Division, National Dairy Research Institute,

TANNINS Plant Tannins: distinctive group of polyphenolic polymers of relatively high molecular weight (M.W = 1000 to 20,000) Further categorized as: HYDROLYSABLE tannins (HTs) or CONDENSED tannins (CTs or Proanthocyandins) on the basis of their structure and reactivity.

HTs are of low M.W ( ) and are polyesters of Gallic acid (gallo tannins) and hexahydroxy-diphenic acid (ellagitannins) with a central polyols such as sugars/glucose and phenolic such as catechin. CTs, M.W ( ) have no carbohydrate core and comprise a group of polyhydroxy-flavan-3-ol oligomers and polymers linked by carbon-carbon bonds between flavanol subunits.

TANNINS (Basic structure) Hydrolysable Tannins o o oHoH o o oHoH oHoH oHoH oHoH Glucose o oo Glucose oHoH oHoH oHoH oHoH oHoH oHoH Gallotannins Ellagitannins oHoH o Catechin OH oHoH Condensed Tannins

Cardiovascular disease, principally heart disease and stroke, are the leading cause of mortality in both men and women in all racial and ethnic groups. The risk of atherosclerosis is increased by high blood pressure, hypertension, kidney disorders, obesity, diabetes, smoking, excessive alcohol consumption, stress, thyroid and adrenal gland problems, and lipid disorders (Crespy and Williamson 2004)

Tea contains many compounds, especially poly- phenols and epidemiologically studies show that polyphenolic compounds present in tea reduces the risk of a variety of diseases. Catechins are the main compounds in green tea; they consist of (-)-epicatechin, (-)-epicatechin-3- gallate (ECg), (-)-epigallocatechin, (-)- epigallocatechin-3-gallate (EGCg) etc. (Graham, 1992)

Monomers (catechin, epicatechin, gallic and ellagic acid) of Tannin present in red wine/ green tea improve the antioxidative / immune status of the animals/ human. (Percival et al., 2002) Epidemiological studies shows that poly-phenolic compounds present in the Tea reduce the risk of a variety of diseases.

THERAPEUTIC VALUES OF TANNIN METABOLITES Mice consumed wine rich in phenolic components as catechin, epicatechin, gallic acid, ellagic acid showed increased antioxidant activity. Gallic acid (GA) also showed strong antioxidant activity by preventing lipid per-oxidation. GA is a strong antioxidant that possesses antimutagenic and anticarcinogenic activities (Shahrzad et. al., 2001)

Green tea contains: (+) – gallocatechin (GC), (-)– epicatechin (EC), (-)– epigallocatechin (EGC), (-)– epicatechingallate (ECG), (-)– epigallocatechingallate (EGCG) which shows numerous biological activities including antibacterial, antioxidant, anti-tumor and cancer preventive activities. Catechin serve as powerful antioxidant against lipid per oxidation when phospholipid bi-layers are exposed to aqueous oxygen radicals.

(+)Catechin prevents cancer (liver, lung, breast and colon cancer) in at least one of three ways: First, they can prevent the formation of carcinogens, Second, they tone up the body's natural detoxification defenses, and Finally, they suppress cancer promotion. (+)Catechin has other promising qualities: antibacterial and antiviral agent, regulating cholesterol and blood pressure, and reducing blood clotting tendencies that may cause heart attacks or strokes

NEUTRACEUTICAL EFFECTS OF CATECHIN AND EPICATECHIN Powerful Antioxidant effect – prevent lipid peroxidation (Terao et al., 1994). Antioxidant activity Scavenge free radicals and reduce oxidative stress. Enzyme induction and enhancing detoxification glutathione peroxidase catalase superoxide dismutase Catechin and epicatechin have Super Oxide Dismutase (SOD) like activity. (Kim et al., 1995)

Cont… Prevent free radical induced RBC hemolysis. (Zhang et al., 1997) Prevent coronary artery disease. (Ishikawa et al., 1997) Inhibit the oxidation of LDL cholesterol, reduced body fat and thereby decrease incidence of heart disease. Catechins may stimulate the secretion of Bile salts and the fecal excretion of cholesterol.

EGCG inhibit phospholipid hydro peroxidation in plasma. Catechin have an anti-hyperglycemic action (Liu et al., 2005) Lowering blood glucose and normalizing insulin release. Prevent cancer (Valcic et al, 1996) – prevent formation of carcinogen, increase the body’s detoxification mechanism against tumor inducing agents.

Inhibition of Onco-gene expression (Liu, 2004) Gallic acid occurs as a free molecule or as part of a tannin molecule. GA is a strong antioxidant that possesses antimutagenic and anticarcinogenic activities (Shahrzad et. al., 2001)

Weight gain, food intake and liver weight of the rates on control and powered green tea (PGT) treatments. (Zhang, et al., 2002) MeasurementControlPGT (2 % in DM) No. of rats10 Initial body weight, g Body wt. gain, g /d Food intake, g /d Liver weight, g /rat

Effect of dietary powered Green tea on serum cholesterol level and Atherogenic Index (A) and on serum triglyceride and lipid peroxide level (B). (Zhang, et al., 2002) A 1. Total cholesterol m mol / l 2. HDL - Ch 3. VLDL + LDL - Ch 4. Atherogenic index B 1. Serum triglyceride 2. Serum lipid peroxide

Plasma cholesterol, TG and oxidative state of plasma lipoprotein in mice fed on atherogenic diet with and without tea extract. (Miura, et al., 2001) ParticularTimeControlTea group (3.2 mg /d) No of mice1617 Body weight, g0, wks Plasma cholesterol, m mol/ l 0, wks Plasma triglyceride, m mol /l Plasma lipid peroxidase, µmol MDA /l

Atheromatous area, aortic weights and aortic lipid contents in mice fed an atherogenic diet with and without tea extract. (Miura, et al., 2001) ParticularsControlTea group% Reduction Atheromatous area, % Aorta, mg Cholesterol, µmol / aorta Triglycerides, µmol / aorta

Composition of Phenolic Compounds in Tea extract (Miura, et al., 2001) CatechinsMg/ g (-)Epigallocatechin-gallate (EGCg)584 (-) Epigallocatechin (EGC)117 (-) Epicatechin (EC)66 (-)Gallocatechingallate (GCg)16 (-)Epicatechin-gallate (ECg)5 Caffeine.4

Varying level of Potency among Catechins. A in vivo experiment indicated that the components of tea catechins possess varying inhibitory effects on Cu 2+ - mediated oxidation of LDL in the following order: EGCg > ECg > EC > C > EGC (Miura, et al., 1994 & 2001)

Catalase protein expression in rats at 16 wks of age that consumed water (control), Black tea polyphenols, Green tea polyphenols for 3 wks (Negishi, et al., 2004) Extract was having tea Polyphenols 5 g /l of water. And water consumption was 30 ml /d

Catechin feeding effects on plasma TAS in rats (pietta, et al., 1998) TreatmentTAS (total antioxidant status), m moles/ l Control1.5 ± 0.3 Catechin (2.1 g /l)3.5 ± 0.3

Colon Cu-Zn SOD in rats given catechin (pietta, et al., 1998)

Mg/Liter Muscadine Wine Total Phenols 834 Gallic acid 14 Ellagic acid 8 Catechin 5 Epicatechin 22 B3 procyanidin 0.3 Composition of Phenolic Compounds in Muscadine Wine ( Percival et al.,2002)

Total antioxidant capacity of plasma of mice consuming red muscadine wine or ethanol 1 : Muscadine wine 2 : Ethanol (Percival et al.,2002)

Catechins hypothesized to help protect against various diseases by contributing, along with antioxidant vitamins (i.e. Vit. C & E) and enzymes (i.e. SOD and Catalase) In vivo studies show that green tea catechins increase total plasma antioxidant activity. Intake of Green tea extract also increases the activity of SOD in serum and the expression of catalase in the aorta. Malondialdehyde, marker of oxidative stress, decreases after Green tea intake

Catechins have a direct (antioxidant) or indirect (increase of activity or expression) effect. Because catechins can act as antioxidant in vitro, they might prevent the oxidation of other antioxidants, such as vitamin E. In some cases ingestion of green tea catechins does not modify the plasma status of vitamin E and C in vivo Catechins increase vitamin E concentration in LDL and in this way could protect LDL against peroxidation.

Glucose concentration affected by Tannic acid (Liu et al., 2005)

In an oral Glucose tolerance test in rats, tea catechins decreased plasma insulin levels but did not affect plasma glucose levels. In type 2 diabetes, lipid metabolism is modified: Plasma and Liver triglyceride levels and plasma cholesterol levels are elevated, GTE intake reduced these values in rats fed a sucrose-rich diet. Catechins also reduced plasma TG levels.

Tannic acid (TA) induces glucose transport through activation of the Insulin-mediated signaling pathways in adipocytes. TA inhibited the expression of key genes for adipogenesis, and has an insulin-like glucose transport stimulatory activity in adipocytes. Epigallocatechin gallate (EGCG) enhances oral glucose tolerance in severely diabetic mice and in moderately diabetic rats.

CONCLUSION Tannins & its monomers have profound effects on health. Not advisable to take a large quantity of tannins, as they may be toxic. It is important to determine the correct dosage of tannins for promoting optimal health.