Health related effects of Tamarind
2.1. Gastrointestinal system and related disorders
2.1.1. Laxative
Tamarind fruit is used as a laxative in traditional medicine because of its high malic acid, tartaric acid and potassium content[1, 2].

2.1.2. Abdominal pain, diarrhea and dysentery
There are various reasons of abdominal pain. Mostly encountered reasons are diarrhea and constipation. For diarrhea Tamarind leaves, for constipation Tamarind fruit, for abdominal pain soft parts of bark and root can be used[1, 2].

2.1.3. Peptic ulcer
Peptic ulcer (mucosal damage deeper than 0.5 centimeters) is painful gastrointestinal damage in stomach and duodenum. It has been shown that Tamarind seed extract has dose dependent protective effect on ulcer models induced by ibuprofen, alcohol and pylorus ligation. It is a possible new ulcer treatment[8]. The protective effect of Tamarind seed comes from its polyphenolic compounds, mainly procyanidin, epicatechin and polymeric tannins. These compounds have anti oxidant effect and protective role against free radicals. Tannins also prevent the ulcer development via causing protein accumulation and vasoconstriction[8].

2.1.4. Spasmolytic effect
Tamarind fruit content cause smooth muscle relaxation via calcium channel blockage. It also explains the usage of Tamarind in diarrhea treatment[9].

2.2. Cancer
Ameliorative effect of Tamarind seed extract has been shown in chemical induced acute nephrotoxicity and renal cell carcinoma. This effect can be explained by antioxidant effect. Although oxidative damage is strongly associated with cancer; polyphenol compounds [2-hydroxy-dihydroxyacetophenone, methyl 3,4-dihydroxybenzoate, 3,4-dihydroxyphenylacetate, (-)-epicatechin, tannin, anthocyanidine and oligomeric proantocyanidins] in Tamarind seed extract has antioxidant enzyme induction properties and cancer related signal pathway blockage effect[10].

2.3. Antimicrobial, antiparasitic, antifungal, antiviral, antinematodal features
Increasing antibiotic resistance among bacteria and toxic effects of antibiotics cause seeking of new effective agents. Medicinal plants are preferred by people because of their easy tolerability. Tamarind is a potential antimicrobial agent[11].

Tamarind extract has antibacterial properties against Burkholderia pseudomallei, Klebsiella pneumoniae, Salmonella paratyphi, Bacillus subtilis, Salmonella typhi, Escherichia coli and Staphylococcus aureus[1, 2, 3, 12, 13, 14]. Antibacterial effect of this plant is linked with its lupeol content[12].

bark extTamarindract showed 25% chemical inhibitory effect on Salmonella typhi. In the phytohemagglutinin presence or absence, it shows lymphoproliferative effect. It is commonly used for so many infectious state including malaria and it stimulates the immune system and act on parasitemia[15]. Tannin was also found in T. indica that its antiparasitic effect via binding the free proteins in the gastrointestinal canal of the parasite or glycoproteins found outside the parasite and cause the death of it. Studies done by bark and leaf extract of T. indica showed its effectiveness and they suggested the usage as an antiparasitic agent[16]. Fruits of Tamarind are used as an antipyretic and leaves of it used in malaria treatment[1, 2]. Potential antifungal effect of T. indica fruit also has been shown against Aspergillus niger and Candida albicans[3]. It has been reported that T. indica plant extract has antiviral properties against watermelon mosaic virus, cow pea mosaic virus and tobacco mosaic virus and antinematodal properties against Bursaphelenchus xylphilus and molluscisidal properties (due to saponin content) against Bulinus trancatus[3].

2.4. Anti-inflammatory effect
Anti-inflammatory effects of leaves, seeds and other parts of Tamarind has been shown but this effect is not as strong as acetylsalicylic acid[17, 18, 19]. Analgesic effect also has been shown in mechanic, chemical and thermal pain models[19]. It stabilizes the red blood cell membrane and prevents the damage. Additionally it shows anti-inflammatory effect and inhibits the release of PG and NO (diclofenac like effect)[5].

When lysosomal damage occurs, phospholipase A2 appears and stimulates the production of inflammatory agents via hydrolysis of phospholipids. Prevention of cell damage causes cytoplasm content preservation and decreases inflammatory response. Polyphenols and flavonoid content of Tamarind associated with anti-inflammatory and antinociceptive effects[5].

2.5. Antioxidant properties
Antioxidant properties of Tamarind seed and leaves has been shown in many studies[2, 3, 20]. Not only phenolic properties (tannins) of raw seeds but also heat dried seeds has antioxidant properties[21].

Phenol rich food and beverages like red wine, grape seed, green tea and tamarind have hypolipidemic, anti-atherosclerotic, antioxidant, anti-inflammatory and immunomodulatory effect. Tamarind fruit is rich in organic acid, pectin, vitamin, mineral content, polyphenol and flavonoid content. Rich polyphenol content exists in seed and fruit and they show regulatory effect on neutrophils[22].

2.6. Anti-diabetic effect
Diabetes mellitus type 1 and type 2 are caused by damage due to chronic inflammation of pancreatic β-cell island. It causes abnormal insulin release, effects insulin receptor and post receptor events and ends with liver, kidney, eye damage. Tamarind seed extract shows pancreatic β-cell island protective effect with its anti-inflammatory properties, blood glucose regulation, and reversal of damage to pancreatic tissue. These effects are caused by increase in pancreatic intracellular Ca2+ level (insulin like effect) and plasma insulin activity rather than decrease in glucose absorption. It also affects GLUT-2, GLUT-4, SREBP-1c (it increases mRNA concentration in liver) at target tissue[2, 3, 23, 24, 25, 26, 27, 28]. Blood glucose level decrease effect of Tamarind seed extract caused by pancreatic β-cell renewal and increase in glucose entrance to muscle and adipose tissue cells via increase in insulin secretion and inhibition of hepatic gluconeogenesis[25]. With the aid of these effects, polyphenol rich Tamarind seed and extract can be used as nutritional support and can be combined with hypoglycemic agents[25].

Hyperinsulinemia and insulin resistance in fructose fed animals, decreases dehydroepiandrosterone and high density lipoprotein (HDL) levels and increases total cholesterol, very low density lipoprotein, low density lipoprotein (LDL), triglyceride levels. Tamarind seed extract regulates insulin effect and shows ameliorative effect on metabolic syndrome[26]. In the literature, only one case reported with hyperglycemia after taking pill that contains tamarind plant extract but the content of this pill is not really known[29].

2.7. Effects on cardiovascular system
Tamarind fruit is rich in polyphenol and flavonoid. It shows moderate antioxidant effect. Epidemiological studies have shown that flavonoid intake from fruits and vegetables have beneficial effect on cardiovascular health[30]. T. indica fruit shows hypocholesterolemic and antioxidant properties via increasing Apo-A1, ABCG5 and LDL receptor gene expression in liver, and decreasing HMG-CoA reductase and inhibition of MTP gene expression. It increases cholesterol excretion, decreases cholesterol biosynthesis, increases LDL-cholesterol intake from peripheral tissues and prevents triglyceride accumulation in liver. It also prevents LDL-cholesterol oxidative damage, the main risk factor of atherosclerosis[30]. Martinello et al. showed that T. indica fruit extract decreased serum total cholesterol (50%), LDL (73%) and triglyceride (60%) and increased HDL (61%). In high cholesterol diet group, it activates antioxidant defence mechanism and prevents aortic atherosclerosis[31, 32].

Tamarind seed shows antioxidant effect via its flavonoid, tannin, polyphenol, anthocyanin and oligomeric proanthocyanidin content. Polysaccharides isolated from Tamarind seed show the immunomodulatory effect via increasing phagocytosis, inhibiting leukocyte migration and decreases cell proliferation[33]. Triglyceride decreasing effect is associated with epicatechin content of the extract. This compound increases total fatty acid, neutral and acidic sterols excreted via feces and shows its hypolipidemic effect in this way[33].

Tamarind seed and fruit are suggested as a nutritional support in patients with high blood cholesterol levels[30, 31, 32, 33].

2.8. Liver protective effect
Alcohol and other chemicals, environmental, biologic toxins and many other factors are related with liver diseases that are important public health problem. Apoptosis (programmed cell death) is the main mechanism in most of the liver diseases. In acute alcohol induced liver toxicity Tamarind leaves showed anti-apoptotic and liver protective effect. It causes membrane stabilization and decreases glutathione consumption. Additionally, it prevents CASP-3 activation and DNA fragmentation and causes histopathologic amelioration[2, 6].

2.9. Weight control effect
Obesity is the result of increased fat content of body, adipocyte hyperplasia and hypertrophy, and macrophage infiltration in adipose tissue. Many pharmacological agents have been tried, however very little of them could be used safely and most of them has many side effects. In western type fed animal model, T. indica fruit extract showed weight reduction and hypolipidemic properties[34]. It is thought that it shows its effect with increasing dopaminergic transmission, regulating lipid metabolism, decreasing plasma leptin level. Flavonoids and polyphenols could be responsible for weight reduction. On the behalf of weight reductive effect, it shows serum cholesterol and LDL reductive and HDL increasing effect[34, 35]. Increased calorie and fat intake causes increase in blood lipids and hepatosteatosis. Daily Tamarind fruit extract consumption shows reversal of hepatosteatosis[35].

2.10. Effect on fluoride toxicity
Fluoride, especially found in drinking water can be harmful in a dose dependent manner. According to World Health Organization report, optimum fluoride level of drinking water is between 0.5-1.0 mg/L. Above this limit it causes fluoride toxicity[36]. Fluoride toxicity is an important global health problem, in India approximately 66.62 million people are affected. Fluoride may also be found in foods but it is especially found in drinking water. Excess fluoride intake alters gene expression, cell cycle, cell proliferation, cell migration, and has negative effect on respiration, metabolism, ion exchange, changes in cellular level (i.e. secretion, endocytosis, apoptosis, necrosis). Oxidative stress, loss of antioxidant capacity may also cause metabolic problems[37]. Extract obtained from Tamarind leaves ameliorates fluoride toxicity effects via its antiperoxidant and antioxidant properties[37].

Extract obtained from Tamarind fruit decreases plasma fluoride concentration and ameliorates fluoride induced liver and kidney damage[38]. And also it has been shown that after some procedures Tamarind fruit can be used in effective drinking water cleaning from fluoride, nickel and lead[39, 40].
2.11. Other effects of Tamarind

2.11.1. Skin
Tamarind xyloglucan is suggested as a natural additive compound in sun creams because it has been shown that it has immunoprotective and DNA protective effect from ultraviolet damage[41].

2.11.2. Wound healing
Application of some mixtures obtained from leaves and bark of Tamarind tree at the wound area was also reported.

2.11.3. Eye
Tamarind seed polysaccharide is used in eye drops to increase its effective time period because of its mucoadhesive properties. The mixture with hyaluronic acid is used in xerophthalmia and with the aid of timolol it decreases intraocular pressure. Studies reported the effect of it in corneal wound healing especially after surgical procedures[3, 42, 43].

2.11.4. Asthma and cough
It has been reported that Tamarind can be effective in allergic astma and cough via antihistaminic, adaptogenic and mast cell stabilizing effects[2].

2.11.5. Nerve repair
It has been shown that xyloglucan obtained from Tamarind seed serves suitable media for degenerated nerves and aids nerve regeneration[44].

2.11.6. Iron bioavailability
Tuntipopitat et al.[45] reported in their study that Tamarind, on the contrary of other herbs and plants, increases iron bioavailability.

3. Toxicity, side effects and drug interactions
The 2-year follow-up study done by Iida et al.[46] reported that there were no side effects in animals fed with Tamarind seed extract in different doses. Heimbach et al.[47] also reported that there were no change in blood biochemistry, urine analysis, liver function test, body weight in animals fed with Tamarind seed polysaccharide for 28 d. In another study toxic effect is not reported, but increase in white blood cells and thrombocyte is observed[2]. Tamarind seed contain tannin and the other compounds that make the digestion difficult so it is suggested that to consume it after boiling or waiting inside water[3]. And also in long term use because of its acidic content it can cause dental erosion[48]. Ibuprofen and acetylsalicylic acid when consumed with Tamarind can increase their bio-availability and increase the blood levels of them[49, 50].
4. Conclusions

Tamarind is a cheap and easily available plant. It is a rich source of essential amino acids, phytochemicals and vitamins. In traditional medicine, it has so many well known health benefits. With the aid of modern techniques it could be used in evidence based medicine in so many health conditions. There is a need of further investigation about this plant and its potential antioxidant and anti-inflammatory properties that can help in many of the diseases.

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