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Fenugreek (Trigonella foenum-graecum)

Fenugreek (Trigonella foenum-graecum) Image
Synonyms / Common Names / Related Terms
4-hydroxyisoleucine (4-OH-Ile), abish, alholva, bird's foot, bockhornsklover, bockshornsamen, bockshornklee, cemen, chilbe, diosgenin, diosgenin fenegriek, fenogrego, fenugree, fenugreek flour, fenugreek gums, fenugreek leaves, fenugreek seed, fenugreek spouts, fenogreco, fenigreko, fenu-thyme, foenugraeci semen, gorogszena, graine de fenugrec, gray hay, Greek hay seed, griechische Heusamen (German), fieno greco, halba, hilbeh, hulba, hu lu ba, kasoori methi, kozieradka pospolita, kreeka lambalaats, mente, mentikura, mentula, methi, methika, methini, methri, methro, mithiguti, N,N'-dicarbazyl, pazhitnik grecheskiy, penantazi, phenolic acids, protodioscin, sag methi, sambala, sarviapila, shabaliidag, shambelile, star fenugreek, trigonella, Trigonella balansae, Trigonella caerulea, Trigonella foenum-gracecum, Trigonella semen, Trigonella stellata, Trigonella, trigonelline, uluhaal, uwatu, vendayam, venthiam, wheat-fenugreek.

Mechanism of Action


  • Constituents: In laboratory tests, fenugreek has been found to contain 4-hydroxyisoleucine (4-OH-Ile), fat, diosgenin, iron, phenolic acids, protein, and protodioscin.27,28,30,7,31,29
  • Analgesic effects: In a rat study, Trigonella foenum-graecum extract showed analgesic activity, which may be similar to nonsteroidal anti-inflammatory drugs (NSAIDs) via the spinal 5-HT system or purinoceptors.1,12
  • Antiadhesive properties: Bactericidal and anti-adhesive properties against Helicobacter pylori have been studied.5 The bactericidal activity of the extract was assessed by a standard kill-curve with seven strains of H. pylori. The anti-adhesive property was assessed by the inhibition of binding of four strains of FITC-labeled H. pylori to stomach sections. Fenugreek was found to have no bactericidal effect on any of the isolates.
  • Anticarcinogenesis effects: In rats, dietary fenugreek seeds inhibited colon carcinogenesis3 and diosgenin from fenugreek suppressed total colonic aberrant crypt foci formation4. In the seeds, the effect may be due to the fiber, flavonoids, or saponins that modulate beta-glucuronidase and mucinase activities. However, the diosgenin study indicated that the extract inhibited bcl-2 and induced caspase-3 protein expression, thereby inducing apoptosis and inhibiting cell growth. Another study of diosgenin indicates that its activity may be due to inhibition of NF-kappaB-regulated gene expression.27 Another chemical extracted from fenugreek, protodioscin, strongly inhibited growth of HL-60 cells, but had little effect on KATO III cells in vitro.7 Apoptosis in the HL-60 cells seems to have been due to the concentration- and time-dependent fragmentation of DNA by protodiosgenin.
  • In a review article, authors presented evidence that numerous agents such as diosgenin (fenugreek) identified from fruits and vegetables can interfere with several cell-signaling pathways.32 The results of several studies indicate that a diet rich in fresh vegetables protects against several common epithelial neoplasms.33 This probable effect has been related to specific micronutrients contained in vegetables. A case-control study and systematic assessment of the relationship between vegetable intake and the risk of gallbladder cancer was conducted in 153 patients with gallbladder cancer and 153 controls with gallstone disease. Each patient's consumption of vegetables was assessed by using a food frequency questionnaire. The frequency of vegetable consumption was divided into three levels: ≥3 days/week, 1-2 days/week and no or rare consumption. Participants were divided into three groups according to the level of vegetable intake. Odds ratios and 95% confidence intervals were computed for subsequent levels of vegetable consumption compared with the high level of consumption. A low consumption of vegetables showed an increase in odds ratio for gallbladder cancer for almost all the vegetables studied. A significant inverse trend was observed for green leafy vegetables and gallbladder cancer. An inverse association was observed for amaranth with an OR of 3.45 for the low vs. high level of consumption. Corresponding values were 2.14 for spinach, 1.86 for bathua, 1.02 for bengalgram leaves, 2.26 for cabbage, 3.06 for fenugreek leaves, 1.95 for mustard leaves and 1.44 for radish leaves. An inverse relationship between the risk of gallbladder cancer and the level of vegetable consumption was observed.
  • Antioxidant activity: In an ethanol toxicity rat study, an aqueous extract of fenugreek seeds prevented the rise in lipid peroxidation and enhanced antioxidant potential.9 These results are supported by in vitro evidence in diabetic human erythrocytes, that polyphenol acids from fenugreek seeds showed a concentration-dependent inhibition of lipid peroxidation.2
  • Antiplatelet activity: In a rat study, a fenugreek extract inhibited ADP (10-5M) induced platelet aggregation (IC50=1.28mg/mL).12
  • Exercise recovery effects: In trained male cyclists, a glucose beverage and 4-hydroxyisoleucine isolated from fenugreek seeds significantly increased muscle glycogen concentration 63% from immediately post exercise to four hours after exercise compared to the control.28
  • Hepatoprotective activity: In an in vitro study using Chang liver cells treated with ethanol, a polyphenolic extract of fenugreek seeds significantly and dose-dependently increased cell viability by reducing oxidation and apoptosis.8
  • Hypoglycemic effects: Hypoglycemic effects of fenugreek observed in animal studies have been associated with a fraction that contains the testa and endosperm of the defatted seeds, called the "A" subfraction. These effects have not been observed with lipid extracts.34,35 Hypoglycemic effects have been attributed to several mechanisms: Sauvaire et al. demonstrated that the amino acid 4-hyroxyisoleucine in fenugreek seeds increases glucose-induced insulin release in vitro in human and rat pancreatic islet cells.16 This amino acid appeared to act only on pancreatic beta cells, since somatostatin and glucagon were not altered in the study. However, another in vitro study indicates that fenugreek seed extract phosphorylates a number of proteins, including the insulin receptor, insulin receptor substrate 1 and p85 subunit of PI3-K, in both 3T3-L1 adipocytes and human hepatoma cells, HepG2.17 These results suggest that fenugreek's effects may be due to activation of the insulin-signaling pathway in adipocytes and liver cells. In human studies, fenugreek reduced the area under the plasma glucose curve (AUC) and increased the number of insulin receptors via an unclear mechanism.10 Also, a combination of bittergourd, jamun seeds, and fenugreek seeds significantly reduced fasting and postprandial glucose level of the diabetic patients15. Fenugreek seeds have also been postulated to exert hypoglycemic effects by stimulating glucose-dependent insulin release by beta cells13, or via inhibition of α-amylase and sucrase activity14. A unique major free amino acid, 4-hydroxyisoleucine (4-OH Ile), has also been characterized as one of the active ingredients for blood glucose control.11
  • Insulin sensitization effects: When administered to type 2 diabetic rats, the amino acid 4-hydroxyisoleucine extracted from fenugreek seeds increased peripheral glucose utilization and decreased hepatic glucose production, thereby improving insulin resistance.6 Chronic ingestion of 4-hydroxyisoleucine significantly reduced insulinemia.
  • Lipid-lowering effects: In animal studies, fenugreek has been found to lower triglycerides, total cholesterol, and low density lipoprotein (LDL) levels.18,19,20,21,22 These effects may be due to saponins, a class of molecule present in fenugreek that is transformed in the gastrointestinal tract to sapogenins. Sapogenins increase biliary cholesterol secretion, potentially leading to lower serum cholesterol levels.23,18,24,25 Based on another in vitro study, fenugreek may increase intra-luminal binding of cholesterol, which results in increased fecal excretion of bile acids and neutral sterols.26


  • Pharmacokinetic data are not available for all components of fenugreek, or for the compound as a whole. Saponins present in fenugreek are believed to be primarily absorbed in the terminal ileum.36
  • In a rabbit study by Zhao et al., after post-intragastric injection of fenugreek extract, the pharmacokinetic parameters of one compartment model were half-life, t½ (Ka) = 0.9 hr, t½ (Ke) = 2.2hr, volume of distribution = 0.64L/kg and AUC = 1.93mg*min/L.37 After intravenous injection, the two compartment open model parameters were t½ (Ka) =10.8 min, t½ (Ke) = 44 min, K2,1 = 0.044/min, K1,0 = 0.026 min, K1,2 = 0.017/min, and the AUC = 931mg*min/L.


  1. Parvizpur, A., Ahmadiani, A., and Kamalinejad, M. Spinal serotonergic system is partially involved in antinociception induced by Trigonella foenum-graecum (TFG) leaf extract. J Ethnopharmacol 2004;95(1):13-17. 15374601
  2. Kaviarasan, S., Vijayalakshmi, K., and Anuradha, C. V. Polyphenol-rich extract of fenugreek seeds protect erythrocytes from oxidative damage. Plant Foods Hum Nutr 2004;59(4):143-147. 15678722
  3. Devasena, T. and Menon, V. P. Fenugreek affects the activity of beta-glucuronidase and mucinase in the colon. Phytother Res 2003;17(9):1088-1091. 14595593
  4. Raju, J., Patlolla, J. M., Swamy, M. V., and Rao, C. V. Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells. Cancer Epidemiol Biomarkers Prev 2004;13(8):1392-1398. 15298963
  5. O'Mahony, R., Al Khtheeri, H., Weerasekera, D., Fernando, N., Vaira, D., Holton, J., and Basset, C. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori. World J Gastroenterol 12-21-2005;11(47):7499-7507. 16437723
  6. Broca, C., Breil, V., Cruciani-Guglielmacci, C., Manteghetti, M., Rouault, C., Derouet, M., Rizkalla, S., Pau, B., Petit, P., Ribes, G., Ktorza, A., Gross, R., Reach, G., and Taouis, M. Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat. Am J Physiol Endocrinol Metab 2004;287(3):E463-E471. 15082420
  7. Hibasami, H., Moteki, H., Ishikawa, K., Katsuzaki, H., Imai, K., Yoshioka, K., Ishii, Y., and Komiya, T. Protodioscin isolated from fenugreek (Trigonella foenumgraecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III. Int J Mo Med 2003;11(1):23-26. 12469212
  8. Kaviarasan, S., Ramamurty, N., Gunasekaran, P., Varalakshmi, E., and Anuradha, C. V. Fenugreek (Trigonella foenum graecum) seed extract prevents ethanol-induced toxicity and apoptosis in Chang liver cells. Alcohol Alcohol 2006;41(3):267-273. 16574673
  9. Thirunavukkarasu, V., Anuradha, C. V., and Viswanathan, P. Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity. Phytother Res 2003;17(7):737-743. 12916070
  10. Raghuram TC, Sharma RD, Sivakumar B, and et al. Effect of fenugreek seeds on intravenous glucose disposition in non-insulin dependent diabetic patients. Phytotherapy Research 1994;8(2):83-86.
  11. Flammang, A. M., Cifone, M. A., Erexson, G. L., and Stankowski, L. F., Jr. Genotoxicity testing of a fenugreek extract. Food Chem Toxicol 2004;42(11):1769-1775. 15350674
  12. Parvizpur, A., Ahmadiani, A., and Kamalinejad, M. Probable role of spinal purinoceptors in the analgesic effect of Trigonella foenum (TFG) leaves extract. J Ethnopharmacol 3-8-2006;104(1-2):108-112. 16298092
  13. Ajabnoor MA and Tilmisany AK. Effect of trigonella foenum graecum on blood glucose levels in normal and alloxan-diabetic mice. J Ethnopharm 1988;22:45-49.
  14. Amin R, Abdul-Ghani AS, and Suleiman MS. Effect of Trigonella feonum graecum on intestinal absorption. Proc. of the 47th Annual Meeting of the American Diabetes Association (Indianapolis USA). Diabetes 1987;36(Supp 1):211a.
  15. Kochhar, A. and Nagi, M. Effect of supplementation of traditional medicinal plants on blood glucose in non-insulin-dependent diabetics: a pilot study. J Med Food 2005;8(4):545-549. 16379570
  16. Sauvaire, Y., Petit, P., Broca, C., Manteghetti, M., Baissac, Y., Fernandez-Alvarez, J., Gross, R., Roye, M., Leconte, A., Gomis, R., and Ribes, G. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 1998;47(2):206-210. 9519714
  17. Vijayakumar, M. V., Singh, S., Chhipa, R. R., and Bhat, M. K. The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway. Br J Pharmacol 2005;146(1):41-48. 15980869
  18. Stark, A. and Madar, Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats. Br J Nutr 1993;69(1):277-287. 8457534
  19. Petit, P., Sauvaire, Y., Ponsin, G., Manteghetti, M., Fave, A., and Ribes, G. Effects of a fenugreek seed extract on feeding behaviour in the rat: metabolic-endocrine correlates. Pharmacol Biochem Behav 1993;45(2):369-374. 8327543
  20. Al-Habori M, Al-Aghbari AM, and Al-Mamary M. Effects of fenugreek seeds and its extracts on plasma lipid profile: a study on rabbits. Phytother Res 1998;12(8):572-575.
  21. Al-Habori M and Raman A. Antidiabetic and hypocholesterolaemic effects of fenugreek. Phytother Res 1998;12(4):233-242.
  22. Valette, G., Sauvaire, Y., Baccou, J. C., and Ribes, G. Hypocholesterolaemic effect of fenugreek seeds in dogs. Atherosclerosis 1984;50(1):105-111. 6696779
  23. Sauvaire, Y., Ribes, G., Baccou, J. C., and Loubatieres-Mariani, M. M. Implication of steroid saponins and sapogenins in the hypocholesterolemic effect of fenugreek. Lipids 1991;26(3):191-197. 2046485
  24. Varshney IP and Sharma SC. Saponins and sapogenins: part XXXII. Studies on Trigonella foenum-graecum Linn. Seeds. J Indian Chem Soc 1966;43(8):564-567.
  25. Yoshikawa, M., Murakami, T., Komatsu, H., Murakami, N., Yamahara, J., and Matsuda, H. Medicinal foodstuffs. IV. Fenugreek seed. (1): structures of trigoneosides Ia, Ib, IIa, IIb, IIIa, and IIIb, new furostanol saponins from the seeds of Indian Trigonella foenum-graecum L Chem Pharm Bull (Tokyo) 1997;45(1):81-87. 9023970
  26. Venkatesan, N., Devaraj, S. N., and Devaraj, H. Increased binding of LDL and VLDL to apo B,E receptors of hepatic plasma membrane of rats treated with Fibernat. Eur J Nutr 2003;42(5):262-271. 14569407
  27. Shishodia, S. and Aggarwal, B. B. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression. Oncogene 3-9-2006;25(10):1463-1473. 16331273
  28. Ruby, B. C., Gaskill, S. E., Slivka, D., and Harger, S. G. The addition of fenugreek extract (Trigonella foenum-graecum) to glucose feeding increases muscle glycogen resynthesis after exercise. Amino Acids 2005;28(1):71-76. 15719265
  29. Yadav, S. K. and Sehgal, S. Effect of domestic processing and cooking methods on total, HCl extractable iron and in vitro availability of iron in bathua and fenugreek leaves. Nutr Health 2003;17(1):61-63. 12803282
  30. Singh, U. P., Singh, D. P., Maurya, S., Maheshwari, R., Singh, M., Dubey, R. S., and Singh, R. B. Investigation on the phenolics of some spices having pharmacotherapeuthic properties. J Herb Pharmacother 2004;4(4):27-42. 15927923
  31. Hooda, S. and Jood, S. Physicochemical, rheological, and organoleptic characteristics of wheat-fenugreek supplemented blends. Nahrung 2003;47(4):265-268. 13678267
  32. Aggarwal, B. B. and Shishodia, S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 5-14-2006;71(10):1397-1421. 16563357
  33. Rai, A., Mohapatra, S. C., and Shukla, H. S. Correlates between vegetable consumption and gallbladder cancer. Eur J Cancer Prev 2006;15(2):134-137. 16523010
  34. Ribes, G., Sauvaire, Y., Baccou, J. C., Valette, G., Chenon, D., Trimble, E. R., and Loubatieres-Mariani, M. M. Effects of fenugreek seeds on endocrine pancreatic secretions in dogs. Ann Nutr Metab 1984;28(1):37-43. 6703649
  35. Ribes, G., Sauvaire, Y., Da Costa, C., Baccou, J. C., and Loubatieres-Mariani, M. M. Antidiabetic effects of subfractions from fenugreek seeds in diabetic dogs. Proc Soc Exp Biol Med 1986;182(2):159-166. 2871558
  36. Sidhu, G. S. and Oakenfull, D. G. A mechanism for the hypocholesterolaemic activity of saponins. Br J Nutr 1986;55(3):643-649. 3676181
  37. Zhao, H. Q., Qu, Y., Wang, X. Y., Lu, X. Y., Zhang, X. H., and Hattori, M. [Determination of trigonelline by HPLC and study on its pharmacokinetics]. Yao Xue Xue Bao 2003;38(4):279-282. 12889128

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