Trigonelline: An Emerging Paradigm for Effective Therapy in Diabetes Mellitus

Jump To References Section


  • Department of Zoology, Shivaji University, Kolhapur – 416004, Maharashtra ,IN
  • Department of Zoology, Shivaji University, Kolhapur – 416004, Maharashtra ,IN
  • Department of Zoology, Shivaji University, Kolhapur – 416004, Maharashtra ,IN
  • Department of Zoology, Shivaji University, Kolhapur – 416004, Maharashtra ,IN
  • Department of Zoology, Shivaji University, Kolhapur – 416004, Maharashtra ,IN



Diabetes Mellitus, Fenugreek, Hypoglycemic, Trigonelline
Endocrinology, Diabetes


Diabetes Mellitus (DM) is recognized as a critical priority because of its epidemic nature. Successful diabetes treatment is not yet established and nowadays, diabetes is considered a global problem. Recent medications have not proved to be complete treating agents because, until now no one had completely cured diabetes. Current antidiabetic drugs have many undesirable side effects. So, an alternative therapy is required. Nowadays, various plant species are used worldwide as hypoglycemic, antihyperglycemic, antidiabetic and antihyperlipidemic agents. A number of plants contain active metabolites such as alkaloids, flavonoids, glycosides, carotenoids, terpenoids, etc., which are extensively used in antidiabetic drugs. About 400 plant species have been reported as having hypoglycemic activity. From these medicinal plants and their active components, various herbal drugs are being formed. This review aims to understand different plant species used to date for treating diabetes, the therapeutic potential of fenugreek, the active compounds isolated from fenugreek, the chemical structure of trigonelline, therapeutic uses of trigonelline as an antidiabetic agent. Research papers, manuscripts and review papers were searched and relevant contents were studied. One hundred sixty-three papers were included in this review. The review resulted in a better understanding of the use of trigonelline in diabetes treatment.


Download data is not yet available.


Metrics Loading ...




How to Cite

Walvekar, M. V., Jadhav, N. A., Daunde, J. A., Potphode, N. D., & Desai, S. S. (2023). Trigonelline: An Emerging Paradigm for Effective Therapy in Diabetes Mellitus. Journal of Endocrinology and Reproduction, 27(1), 15–28.



Review Article



Ahmed AM. History of diabetes mellitus. Saudi Med J. 2002; 23(4):373-78.

IDF Diabetes Atlas, 10thEd. International Diabetes Federation; 2021.

Madras Diabetes Research Foundation (India), 2014. http://

ICMR Guidelines for Management of Type 2 Diabetes, Indian Council of Medical Research; 2018.

Joshi SR. Metabolic syndrome—emerging clusters of the Indian phenotype. J Assoc Physi Ind. 2003; 51:445–6.

Deepa R, Sandeep S, Mohan V, et al. Abdominal obesity, visceral fat and type 2 diabetes—Asian Indian phenotype, in Type 2 Diabetes in South Asians: Epidemiology, Risk Factors and Prevention. Jaypee Brothers Medical Publishers, New Delhi, India; 2006. pp. 138–52.

Chandalia M, Abate N, Garg AJ, et al. Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999; 84(7):2329–35. jc.84.7.2329 DOI:

Ramachandran A, Snehalatha C, Viswanathan V, et al. Risk of non-insulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: a comparative analysis between Asian Indians, Mexican Americans and Whites. Diab Res Clin Pract. 1997; 36(2):121–5. 8227(97)00040-5 DOI:

Hannan MA, Selim S, Saha M, Miah MA. Screening the Risk Factors of Diabetes Mellitus in 1st year MBBS and BDS Students of a Medical College in Bangladesh. J Endocrinol Reprod. 2022; 26(2):119-26.

Madiraju AK, Erion DM, Rahimi Y, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014; 510:542–6. DOI:

Kiersztan A, Modzelewska A, Jarzyna R, et al. Inhibition of gluconeogenesis by vanadium and metformin in kidney- cortex tubules isolated from control and diabetic rabbits. Biochem Pharmacol. 2002; 63:1371–82. https:// DOI:

Cornell S. Type 2 Diabetes Treatment Recommendations Update: Appropriate Use of Dipeptidyl Peptidase-4 Inhibitors. J Diabetes Metab. 2014; 05:8. https://doi. org/10.4172/2155-6156.1000414 DOI:

Lawal HA, Atiku MK, Khelpai DG, Wannang NN. Hypoglycaemic and hypolipidaemic effect of aqueous leaf extract of Murraya koenigii in normal and alloxandiabetic rats. Niger J Physiol Sci. 2008; 23:37–40. https:// DOI:

Kasiviswanath R, Ramesh A, Kumar KE. Hypoglycemic and antihyperglycemic effect of Gmelina asiatica Linn. in normal and in alloxan induced diabetic rats. Biol Pharm Bull. 2005; 28(4):729–32. bpb.28.729 DOI:

Akhtar FM, Ali MR. Study of the anti diabetic effect of a compound medicinal plant prescription in normal and diabetic rabbit. J Pakistan Med Assoc. 1984; 34:239-44.

Brinker FJ. Herb contraindications and drug interactions: With appendices addressing specific conditions and medicines. 2nd ed. Oregon (USA): Eclectic Medical Publications; 1998.

Pepato MT, Baviera AM, Vendramini RC, et al., Cissus sicyoides (princess vine) in the long-term treatment of streptozotocin-diabetic rats. Biotechnol Appl Biochem. 2003; 37:15-20. DOI:

Sudha P, Zinjarde SS, Bhargava SY, Kumar AR. Potent α-amylase inhibitory activity of Indian Ayurvedic medicinal plants. BMC Complement Altern Med. 2011; 11(5):1-10. DOI:

Mootoosamy A, Mahomoodally MF. Ethnomedicinal application of native remedies used against diabetes and related complications in Mauritius. J Ethnopharmacol. 2014; 151:413–44. 10.069 DOI:

Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol. 1995; 48:25–32. https://doi. org/10.1016/0378-8741(95)01279-M DOI:

Sukandar EY, Adnyana IK, Nurfitria RS. Antioxidant potential of garlic and turmeric mixture - A traditional Indonesian formulation. Indian J Trad Knowl. 2015; 14:632–6.

Moradabadi L, Kouhsari SM, Sani MF. Hypoglycemic effects of three medicinal plants in experimental diabetes: Inhibition of rat intestinal α-glucosidase and enhanced pancreatic insulin and cardiac GLUT-4 mRNAs expression. Iran J Pharm Res. 2013; 12:385–97.

Mesa MG. Hypolipidemic potential of plants used in Cuba. Pharmacologyonline 2014; 1:73–80.

Karou SD, Tchacondo T, Tchibozo MAD, et al. Ethnobotanical study of medicinal plants used in the management of diabetes mellitus and hypertension in the Central Region of Togo. Pharm Biol. 2011; 49:1286– 97. DOI:

Xie W, Du L. Diabetes is an inflammatory disease: Evidence from traditional Chinese medicines. Diabetes Obes Metab. 2011; 13:289–301. j.1463-1326.2010.01336.x DOI:

Kaleem M, Asif M, Ahmed QU, Bano B. Antidiabetic and antioxidant activity of Annona squamosa extract in streptozotocin-induced diabetic rats. Singapore Med J. 2006; 47:670–5.

Gupta RK, Kesari AN, Murthy PS, et al. Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals. J Ethnopharmacol. 2005; 99:75–81. https://doi. org/10.1016/j.jep.2005.01.048 DOI:

Gupta RK, Kesari AN, Watal G, et al. Nutritional and hypoglycemic effect of fruit pulp of Annona squamosa in normal healthy and alloxan-induced diabetic rabbits. Ann Nutr Metab. 2005; 49:407-13. https://doi. org/10.1159/000088987 DOI:

Chempakam B. Hypoglycemic activity of arecoline in betel nut Areca catechu L. Indian J Exp Biol. 1993; 31:474–5.

Subramonium A, Pushpangadan P, Rajasekharan A, et al. Effects of Artemisia pallens Wall. On blood glucose levels in normal and alloxan-induced diabetic rats. J Ethnopharmacol.1996; 50:13–7. https://doi. org/10.1016/0378-8741(95)01329-6 DOI:

Pari L, Amarnath Satheesh M. Antidiabetic activity of Boerhavia diffusa L. effect on hepatic key enzymes in experimental diabetes. J Ethnopharmacol. 2004; 91:109– 13. DOI:

Satheesh MA, Pari L. Antioxidant effect of Boerhavia diffusa L. in tissues of alloxan induced diabetic rats. Indian J Exp Biol.2004; 42:989–92.

Pari L, Amarnath Satheesh M. Antidiabetic effect of Boerhavia diffusa: effect on serum and tissue lipids in experimental diabetes. J Med Food. 2004; 7:472–6. DOI:

Arora S, Haldar C, Basu P, et al. Oral Administration of Root Extract of Boerhaavia diffusa Mitigates Diabetesinduced Kidney Damages in the Golden Hamster Mesocricetus auratus. J Endocrinol Reprod. 2022; 26(3):163-170.

Arora S, Haldar C. Diabetes: Rescue by Boerhaavia diffusa. J Endocrinol Reprod. 2018; 22(2):1-3.

Saleem R, Ahmad M, Hussain SA, et al. Hypotensive, hypoglycemic and toxicological studies on the flavonol C-glycoside shamimin from Bombax ceiba. Planta Med. 1999; 5:331–4. DOI:

Somani R, Kasture S, Singhai AK. Antidiabetic potential of Butea monosperma in rats. Fitoterapia. 2006; 77:86– 90. DOI:

Chakrabarti S, Biswas TK, Seal T, et al. Antidiabetic activity of Caesalpinia bonducella F. in chronic type 2 diabetic model in Long-Evans rats and evaluation of insulin secretagogue property of its fractions on isolated islets. J Ethnopharmacol. 2005; 97:117–22. https://doi. org/10.1016/j.jep.2004.10.025 DOI:

Chakrabarti S, Biswas TK, Rokeya B, et al. Advanced studies on the hypoglycemic effect of Caesalpinia bonducella F. in type 1 and 2 diabetes in Long Evans rats. J Ethnopharmacol. 2003; 84:41–46. https://doi. org/10.1016/S0378-8741(02)00262-3 DOI:

Sharma SR, Dwivedi SK, Swarup D. Hypoglycemic, antihyperglycemic and hypolipidemic activities of Caesalpinia bonducella seeds in rats. J Ethnopharmacol. 1997; 58:39–44. 00079-2 DOI:

Gomes A, Vedasiromoni JR, Das M, et al. Antihyperglycemic effect of black tea (Camellia sinensis) in rats. J Ethnopharmacol. 1995; 45:223– 226. https:// DOI:

Devasagayam TPA, Kamat JP, Mohan H, Kesavan PC. Caffeine as an antioxidant: Inhibition of lipid peroxidation induced by reactive oxygen species in rat liver microsomes. Biochim Biophys Acta. 1996; 1282:63–70. DOI:

Agarwal V, Chauhan BM. A study on composition and hypolipidemic effect of dietary fiber from some plant foods. Plant Foods Human Nutr. 1988; 38:189–97. DOI:

Kamble SM, Kamlakar PL, Vaidya S, Bambole VD. Influence of Coccinia indica on certain enzymes in glycolytic and lipolytic pathway in human diabetes. Indian J Med Sci. 1998; 52:143–6.

Kuroda M, Mimaki Y, Nishiyama T, et al., Hypoglycaemic effects of turmeric (Curcumalonga L. rhizomes) on genetically diabetic KK-Ay mice. Biol Pharm Bull. 2005; 28:937-9. DOI:

Lekshmi PC, Arimboor R, Nisha VM, et al. In vitro antidiabetic and inhibitory potential of turmeric (Curcuma longa L.) rhizome against cellular and LDL oxidation and angiotensin converting enzyme. J Food Sci Technol. 2014; 51(12):3910-7. 013-0953-7 DOI:

Bhattacharya A, Chatterjee A, Ghosal S, Bhattacharya SK. Antioxidant activity of active tannoid principles of Emblica officinalis (amla). Indian J Exp Biol. 1999; 37:676–80.

Kumar KCS, Muller K. Medicinal plants from Nepal, II. Evaluation as inhibitors of lipid peroxidation in biological membranes. J Ethnopharmacol. 1999; 64:135–9. DOI:

Devasagayam TPA, Subramanian M, Singh BB, et al. Protection of plasmid pBR322 DNA by flavonoids against single-strand breaks induced by singlet molecular oxygen. J Photochem Photobiol. 1995; 30:97–103. DOI:

Maroo J, Vasu VT, Gupta S. Dose-dependent hypoglycemic effect of aqueous extract of Enicostemma littorale blume in alloxan-induced diabetic rats. Phytomedicine. 2003; 10:196–9. https://doi. org/10.1078/094471103321659933 DOI:

Vijayvargia R, Kumar M, Gupta S. Hypoglycemic effect of aqueous extract of Enicostemma littorale Blume (chhota chirayata) on alloxan induced diabetes mellitus in rats. Indian J Exp Biol. 2000; 38:781–4.

Arai I, Amagaya S, Komatzu Y, et al. Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice. J Ethnopharmacol. 1999; 68:307–14. 8741(99)00066-5 DOI:

Augusti KT, Daniel RS, Cherian S, et al. Effect of Leucoperalgonin derivative from Ficus benghalensis Linn. on diabetic dogs. Indian J Med Res. 1994; 99:82–6.

Chattopadhyay RR. A comparative evaluation of some blood sugar lowering agents of plant origin. J Ethnopharmacol. 1999; 67:367–72. https://doi. org/10.1016/S0378-8741(99)00095-1 DOI:

Preuss HG, Jarrell ST, Scheckenbach R, et al. Comparative effects of chromium, vanadium and Gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr. 1998; 17:116–23. 07315724.1998.10718736 DOI:

Khanna P, Jain SC, Panagariya A, Dixit VP. Hypoglycemic activity of polypeptide-p from a plant source. J Nat Prod. 1981; 44:648–55. DOI:

Shibib BA, Khan LA, Rahman R. Hypoglycemic activity of Coccinia indica and Momordica charantia in diabetic rats: Depression of the hepatic gluconeogenic enzymes glucose-6-phosphatase and fructose-1, 6-biphosphatase and elevation of liver and red-cell shunt enzyme glucose-6-phosphate dehydrogenase. Biochem J. 1993; 292:267–70. DOI:

Nagaraju N. Biochemical studies on some medicinal plants of Rayalaseema region. PhD thesis. SV University, Tirupathi, 1992.

Rao BK, Kessavulu MM, Giri R, Apparao C. Antidiabetic and hypolipidemic effects of Momordica cymbalaria Hook fruit powder in alloxan-diabetic rats. J Ethnopharmacol. 1999; 67:103–9. https://doi. org/10.1016/S0378-8741(99)00004-5 DOI:

Khan BA, Abraham A, Leelamma S. Hypoglycemic action of Murraya koenigii (curry leaf) and Brassica juncea (mustard) mechanism of action. Indian J Biochem Biophys. 1995; 32:106–108.

Dhanabal SP, Sureshkumar M, Ramanathan M, Suresh B. Hypoglycemic effect of ethanolic extract of Musa sapientum on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential. J Herb Pharmacother. 2005; 5:7–19. J157v05n02_02 DOI:

Pari L, Umamaheswari J. Antihyperglycaemic activity of Musa sapientum flowers: effect on lipid peroxidation in alloxan diabetic rats. Phytother Res. 2000; 14:136–138. 1573(200003)14:2<136::AID-PTR607>3.0.CO;2-K DOI:<136::AID-PTR607>3.0.CO;2-K

Pari L, Maheswari JU. Hypoglycemic effect of Musa sapientum L. in alloxan-induced diabetic rats. J Ethnopharmacol. 1999; 68:321–5. https://doi. org/10.1016/S0378-8741(99)00088-4 DOI:

Tormo MA, Gil-Exojo I, Romero de Tejada A, Campillo JE. Hypoglycemic and anorexigenic activities of an alpha-amylase inhibitor from white kidney beans (Phaseolus vulgaris) in Wistar rats. Br J Nutr. 2004; 92:785– 90. DOI:

Pari L, Venkateswaran S. Protective role of Phaseolus vulgaris on changes in the fatty acid composition in experimental diabetes. J Med Food. 2004; 7:204–9. DOI:

Knott RM, Grant G, Bardocz S, et al., Alterations in the level of insulin receptor and GLUT-4 mRNA in skeletal muscle from rats fed a kidney bean (Phaseolus vulgaris) diet. Int J Biochem. 1992; 24:897–902. https://doi. org/10.1016/0020-711X(92)90094-H DOI:

Haranath PSRK, Ranganathrao K, Anjaneyulu CR, Ramnathan JD. Studies on the hypoglycemic and pharmacological actions of some stilbenes. Indian J Med Sci. 1958; 12:85–89.

Joglekar GV, Chaudhary NY, Aiaman R. Effect of Indian medicinal plants on glucose absorption in mice. Indian J Physiol Pharmacol. 1959; 3:76–7.

Chakravarty BK, Gupta S, Gambhir SS, Gode KD. Pancreatic beta cell regeneration. A novel antidiabetic mechanism of Pterocarpus marsupium Roxb. Indian J Pharmacol. 1980; 12:123–7.

Jahromi MA, Ray AB, Chansouria JPN. Antihyperlipidemic effect of flavonoids from Pterocarpus marsupium. J Nat Prod. 1993; 56:989–94. https://doi. org/10.1021/np50097a001 DOI:

Pagadala JC, Yenugu S, Gudipalli P. Anti-diabetic Activity of Partially Purified Santalin A from the Heartwood of Pterocarpus santalinus L.f. in Alloxan-induced Diabetic Wistar Rat J Endocrinol Reprod. 2021; 25(1):65-78.

Jafri, M.A., Aslam, M., Javed, K., and Singh, S.: Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan induced diabetic rats. J Ethnopharmacol. 2000; 70:309–14. https://doi. org/10.1016/S0378-8741(99)00170-1 DOI:

Pari L, Latha M. Antidiabetic effect of Scoparia dulcis: effect on lipid peroxidation in streptozotocin diabetes. Gen Physiol Biophys. 2005; 24:13–26.

Pari L, Latha M. Antihyperlipidemic effect of Scoparia dulcis (sweet broomweed) in streptozotocin diabetic rats. J Med Food. 2006; 9:102–107. jmf.2006.9.102 DOI:

Latha M, Pari L, Sitasawad S, Bhonde, R. Insulin secretagogue activity and cytoprotective role of the traditional antidiabetic plant Scoparia dulcis (Sweet Broomweed). Life Sci. 2004; 75:2003–14. lfs.2004.05.012 DOI:

Saxena AM, Bajpai MB, Murthy PS, Mukherjee SK. Mechanism of blood sugar lowering by a Swerchirin containing hexane fraction (SWI) of Swertia chirayita. Indian J Exp Biol. 1993; 31:178–81.

Rao BK, Rao CH. Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats. Phytomedicine. 2001; 8: 88–93. 00015 DOI:

Sabu MC, Kuttan R. Antidiabetic activity of medicinal plants and its relationship with their antioxidant property. J Ethnopharmacol. 2002; 81:155–60. https://doi. org/10.1016/S0378-8741(02)00034-X DOI:

Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. J Ethnopharmacol. 2003, 84:105–8. https://doi. org/10.1016/S0378-8741(02)00144-7 DOI:

Dineshkumar B, Analava M, Manjunatha M. Antidiabetic and hypolipidaemic effects of few common plants extract in type 2 diabetic patients at Bengal. Int J Diabetes Metabol. 2010; 18:59–65. https://doi. org/10.1159/000497694 DOI:

Marwat SK, Fazal UrR, Khan EA, et al. Useful ethnophytomedicinal recipes of angiosperms used against diabetes in South East Asian countries (India, Pakistan and Sri Lanka). Pak J Pharma Sci. 2014; 27:1333–58.

Tanaka M, Kishimoto Y, Saita E, et al. Terminalia bellirica extract inhibits low-density lipoprotein oxidation and macrophage inflammatory response in vitro. Antioxidants. 2016; 5(2):20. antiox5020020 DOI:

Sharma R, Amin H, Galib, Prajapati PK. Antidiabetic claims of Tinospora cordifolia (Willd.) miers: Critical appraisal and role in therapy. Asian Pac J Trop Biomed. 2015; 5:68–78. 1691(15)30173-8 DOI:

Patel MB, Mishra S. Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia. Phytomedicine. 2011; 18:1045–52. 2011.05.006 DOI:

Thomas A, Rajesh EK, Kumar DS. The significance of Tinospora crispa in treatment of diabetes mellitus. Phytother Res. 2016; 30:357–66. ptr.5559 DOI:

Sauvaire Y, Petit P, Broca C, et al. 4-hydroxyisoleucine: A novel amino acid potentiator of insulin secretion. Diabetes. 1998; 47(2):206–10. diab.47.2.206 DOI:

Khosla P, Gupta DD, Nagpal RK. Effect of Trigonella foenum graecum (fenugreek) on blood glucose in normal and diabetic rats. Indian J Physiol Pharmacol. 1995; 39:173–4.

Gupta D, Raju J, Baquer NZ. Modulation of some gluconeogenic enzyme activities in diabetic rat liver and kidney: Effect of antidiabetic compounds. Indian J Exp Biol. 1999; 37:196–9.

Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats. Phytother Res. 1999; 13:197–201. https://doi. org/10.1002/(SICI)1099-1573(199905)13:3<197::AIDPTR413> 3.0.CO;2-L DOI:<197::AID-PTR413>3.0.CO;2-L

Dixit PP, Ghaskadbi SS, Hari M, Devasagayam TPA. Antioxidant properties of germinated fenugreek seeds. Phytother Res. 2005; 19:977–83. ptr.1769 DOI:

Adallu B, Radhika B. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Indian J Exp Biol. 2000; 38:607– 9.

Arora S, Haldar C. Phytomelatonin (Zea mays) Supplementation Restores the Damage Caused by Induced-Diabetes in the Golden Hamster Mesocricetus auratus. J Endocrinol Reprod. 2020; 24(2):81-6.

Ranilla LG, Kwon YI, Apostolidis E, Shetty K. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America. Bioresour Technol. 2010; 101:4676–89. biortech.2010.01.093 DOI:

Morakinyo AO, Akindele AJ, Ahmed Z. Modulation of antioxidant enzymes and inflammatory cytokines: Possible mechanism of anti-diabetic effect of ginger extracts. Afr J Biomed Res. 2011; 14:195–202.

Prajapati ND, Purohit SS, Sharma AK, Kumar T. A Handbook of Medicinal Plants: A Complete Source Book. Jodhpur (India): Agrobios Publisher; 2003. 523 p.

Sharma R. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr Res. 1986; 6:1353-64. S0271-5317(86)80020-3 DOI:

Petropoulos GA. Fenugreek: the genus Trigonella. CRC. 2002; 11:1-201.

Deshmukh VM, Walvekar MV, Desai SR. Modulatory effect of fenugreek (Trigonella foenum graceum) seed extract on salivary glands lipofuschinogenesis in aging accelerated male mice. Int J Pharm Bio Sci. 2014; 5(2):83-9.

Deshmukh VM, Walvekar MV, Khairmode SP. Protective role of Trigonella foenum graceum (fenugreek) seed extract on oxidative stress in salivary glands of aging accelerated mice. Arch Appl Sci Res. 2014; 6(1):92-6.

Walvekar MV, Deshmukh VM, Pol SB. Structural and cytochemical study of salivary glands after fenugreek seed extract administration in oxidatively stressed mice. Int J Pharmacogn Phytochem Res. 2015; 7(3):395-400.

Deshmukh VM, Walvekar MV, Desai SS. Effect of Trigonella foenum graceum (fenugreek) -loaded PLGA nanoparticles on non-specific esterase enzyme activity in salivary glands of aging accelerated mice. J Endocrinol Reprod. 2015; 19(1):34-39. jer/2015/v19/86058 DOI:

Deshmukh VM, Walvekar MV, Ghadage YK, Deshpande VY. Protective effect of fenugreek seed extract on lipofuscinogenesis and antioxidative profile in reproductive system of aging accelerated male mice. Int J Curr Biotechnol. 2020; 8(4):1-6.

Walvekar MV, Pol SB, Chandrashekhar Sagar BK. Histopathological and ultrastructural studies of the effect of fenugreek seed extract on pancreas of alloxan induced diabetic mice. Int J Pharm Sci Res. 2014; 5(7):1- 16.

Zhou J, Chan L, Zhou S. Trigonelline: a Plant Alkaloid with Therapeutic Potential for Diabetes and Central Nervous System Disease. Curr Med Chem. 2012; 19:3523- 31. DOI:

Riyad MA, Abdul-Salam SA, Mohammad SS. Effect of Fenugreek and Lupine seeds on the development of experimental diabetes in rats. Planta Med. 1988; 54:286–90. DOI:

Sharma RD, Raghuram TC. Hypoglycaemic effect of fenugreek seeds in non-insulin dependent diabetic subjects. Nutr Res. 1990; 10:731–9. S0271-5317(05)80822-X DOI:

Mitra A, Bhattacharya D. Dose-dependent effects of Fenugreek composite in diabetes with dislipidaemia. Int J Food Safety. 2006; 8:49-55.

Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek in non-insulin dependent diabetics. Eur J Clin Nutr 1988; 42(1):51-4.

Jain V, Jain P, Sharma S, Kakani R. Hypolipidaemic activity of syndrex, a hydroalcoholic extract of fenugreek seeds: Single blind clinical study. Int Med J. 1995; 89:1-41.

Sharma RD, Sarkar A, Hazra DK, et al. Toxicological evaluation of fenugreek seeds: a long term feeding experiment in diabetic patients. Phytother Res. 1996; 10(6):519-20. 1573(199609)10:6<519::AID-PTR873>3.0.CO;2-T DOI:<519::AID-PTR873>3.0.CO;2-T

Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr. 1990; 44(4):301-6.

Raghuram TC, Sharma RD, Sivakumar B, Sahay BK. Effect of fenugreek seeds on intravenous glucose disposition in non-insulin dependent diabetic patients. Phytother Res. 1994; 8(2):83-6. ptr.2650080206 DOI:

Izzo AA, Di Carlo G, Borrelli F, Ernst E. Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction. Int J Card. 2005; 98(1):1-14. https:// DOI:

Petit PR, Sauvaire YD, Hillaire-Buys DM, et al., Steroid saponins from fenugreek seeds: extraction, purification, and pharmacological investigation on feeding behaviour and plasma cholesterol. Steroids. 1995; 60(10):674-80. DOI:

Ribes G, Sauvaire Y, Da Costa C, et al. Antidiabetic effects of subtractions from fenugreek seeds in diabetic dogs. Exp Biol Med. 1986; 182(2):159-66. https://doi. org/10.3181/00379727-182-42322 DOI:

Suja Pandian R, Anuradha CV, Viswanathan P. Gastroprotective effect of fenugreek seeds (Trigonella foenum-graecum) on experimental gastric ulcer in rats. J Ethnopharmacol. 2002; 81(3):393-97. https://doi. org/10.1016/S0378-8741(02)00117-4 DOI:

Thirunavukkarasu V, Anuradha CV, Viswanathan P. Protective effect of fenugreek (Trigonella foenum-graecum) seeds in experimental ethanol toxicity. Phytother Res. 2003; 17:737–43. DOI:

Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plan Food Hum Nutr. 1999; 53(4):359-65. https://doi. org/10.1023/A:1008021618733 DOI:

Xue WL, Li XS, Zhang J, et al. Effect of Trigonella foenum- graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocin- induced diabetic rats. Asia Pac J Clin Nutr. 2007; 1:422–6.

Bin-Hafeez B, Haque R, Parvez S, et al. Immunomodulatory effects of fenugreek (Trigonella foenum-graecum L.) extract in mice. Int Immunopharmacol. 2003; 3:257–65. https://doi. org/10.1016/S1567-5769(02)00292-8 DOI:

Tahiliani P, Kar A. The combined effects of Trigonella and Allium extracts in the regulation of hyperthyroidism in rats. Phytomedicine. 2003; 10:665–8. https://doi. org/10.1078/0944-7113-00277 DOI:

Shabbeer S, Sobolewski M, Anchoori RK, et al. Fenugreek: A naturally occurring edible spice as an anticancer agent. Cancer Biol Ther. 2009; 8(3):272-8. DOI:

Amin A, Alkaabi A, Al-Falasi S, Daoud SA. Chemopreventive activities of Trigonella foenumgraecum (Fenugreek) against breast cancer. Cell Biol Int. 2001; 29:687–94. cellbi.2005.04.004 DOI:

Verma SK, Singh SK, Mathur A. In vitro cytotoxicity of Calotropis procera and Trigonella foenum-graecum against human cancer cell lines. J Chem Pharm Res. 2010; 2:861–5.

Loew D, Kaszkin M. Approaching the Problem of Bioequivalence of Herbal Medicinal Products. Phyther Res. 2002; 16:705–11. DOI:

Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine. 1995; 2(2):137–89. DOI:

Srinivasan K. Fenugreek (Trigonella foenum- graecum): A review of health beneficial physiological effects. Food Rev Intl. 2006; 22:203–24. DOI:

Hidvegi M, El-Kady A, Lasztity R, et al. Contributions to the nutritional characterization of fenugreek (Trigonella foenum-graecum L). Acta Aliment. 1984; 13:315–24.

Fowden L, Pratt H, Smith A. 4-Hydroxyisoleucine from seed of Trigonella foenum-graecum. Phytochem. 1973; 12:1707–11. 9422(73)80391-7 DOI:

Sauvaire Y, Girardon P, Baccou JC, Risterucci AM. Changes in the growth, proteins and free amino acids of developing seed and pod of fenugreek. Phytochem. 1984; 23:479–86. 9422(00)80363-5 DOI:

Birdsong BA, Alston R, Turner BL. Distribution of canavanine in the family leguminosae as related to phyletic groupings. Can J Bot. 1960; 38:499–505. https://doi. org/10.1139/b60-046 DOI:

Parmar VS, Singh S, Rathore JS. A structure revision of trigocoumarin. J Chem Res Synop. 1984; 11:378.

Khurana SK, Krishnamoorthy V, Parmar VS, et al. 3, 4, 7-Trimethylcoumarin from Trigonella foenum-graecum stems. Phytochem. 1982; 21:2145–6. https://doi. org/10.1016/0031-9422(82)83074-4 DOI:

Skaltsa H, Petropoulos GA. Fenugreek—The Genus Trigonella. Taylor and Francis, London and New York. 2002; pp. 132–61. https://doi. org/10.1201/9780203217474 DOI:

Seshadri TR, Varshney IP, Sood AR. Study of glycosides from T. corniculata Linn. and T. foenum-graecum Linn seeds. Curr Sci India. 1973; 42:421–2.

Wagner H, Iyengar MA, Horhammer L. Vicenin-1 and -2 in the seeds of Trigonella foenum-graecum. Phytochem. 1973; 12:2548. 9422(73)80481-9 DOI:

Shang M, Cai S, Han J, et al. Studies on flavonoids from Fenugreek (Trigonella foenum-graecum L.). Zhongguo Zhong Yao Za Zhi. 1998; 23(10):614-6, 39.

Soliman G, Mustafa Z. The Saponin of Fenugreek Seeds. Nature. 1943; 151:195–6. https://doi. org/10.1038/151195b0 DOI:

Zia T, Hasnain SN, Hasan SK. Evaluation of the oral hypoglycaemic effect of Trigonella foenum-graecum L. (methi) in normal mice. J Ethnopharmacol. 2001; 75:191–5. 8741(01)00186-6 DOI:

Nishina Y, Sato K, Shiga K. Proton release from flavoprotein D-amino acid oxidase on complexation with the zwitterionic ligand, trigonelline. Biochemistry. 1990; 107:726-31. jbchem.a123116 DOI:

Allred KF, Yackley KM, Vanamala J, Allred CD. Trigonelline is a novel phytoestrogen in coffee beans. J Nutr. 2009; 139:1833–8. jn.109.108001 DOI:

Tresserra-Rimbau A, Rimm EB, Medina-Remón A, et al. Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study. Nutr Metab Cardiovasc Dis. 2014; 24:639–47. 2013.12.014 DOI:

Czok G. Biopharmacological effects of coffee substances other than caffeine. Arch Sci Med. (Torino) 1974; 131(1):15-7.

Errol Z, Raymond T. Trigonelline. Review of Toxicological Literature. 535-83.

Almeida AA, Farah A, Silva DA, et al. Antibacterial activity of coffee extracts and selected coffee chemical compounds against enterobacteria. J Agric Food Chem. 2006; 54(23):8738-43. jf0617317 DOI:

Ozcelik B, Kartal M, Orhan I. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm Biol. 2011; 49(4):396-402. DOI:

Naito S, Yatagai C, Maruyama M, Sumi H. Effect of coffee extracts on plasma fibrinolysis and platelet aggregation. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2011; 46(2):260-9.

Hirakawa N, Okauchi R, Miura Y, Yagasaki K. Antiinvasive activity of niacin and trigonelline against cancer cells. Biosci Biotechnol Biochem. 2005; 69(3):653-8. DOI:

Anthoni U, Christophersen C, Hougaard L, Nielsen PH. Review: Quaternary ammonium compounds in the biosphere-an example of a versatile adaptive strategy. Comp Biochem Physiol. 1991; 99B(1):1-18. https://doi. org/10.1016/0305-0491(91)90002-U DOI:

Tohda C, Kuboyama T, Komatsu K. Search for natural products related to regeneration of the neuronal network. Neurosignals. 2005; 14(1-2):34-45. https://doi. org/10.1159/000085384 DOI:

Zhou J, Zhou S, Zeng S. Experimental diabetes treated with trigonelline: effect on beta cell and pancreatic oxidative parameters. Fundam Clin Pharmacol. 2013; 27(3):279-87. 8206.2011.01022.x DOI:

Mishkinsky JS, Goldschmied A, Joseph B, et al. Hypoglycaemic effect of Trigonella foenum graecum and Lupinus termis Leguminosae) seeds and their major alkaloids in alloxan-diabetic and normal rats. Arch Int Pharmacodyn Ther. 1974; 210(1):27-37.

Yoshinari O, Sato H, Igarashi K. Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats. Biosci Biotechnol Biochem. 2009; 73(5):1033-1041. bbb.80805 DOI:

Yoshinari O, Igarashi K. Anti-diabetic effect of trigonelline and nicotinic acid, on KK-Ay mice. Curr Med Chem. 2010; 17(20):2196-202. https://doi. org/10.2174/092986710791299902 DOI:

Al-Habori M, Raman A, Lawrence MJ, Skett P. In vitro effect of fenugreek extracts on intestinal sodiumdependent glucose uptake and hepatic glycogen phosphorylase A. Int Exp Diabetes Res. 2001; 2:91-9. DOI:

Abe S, Kaneda T. Effect of betaines and taurine and its derivatives on plasma cholesterol levels in rats. Eiyo To Shokuryo. 1975; 28:125-8. jsnfs1949.28.125 DOI:

Bakuradze T, Lang R, Hofmann T, et al. Antioxidant effectiveness of coffee extracts and selected constituents in cell-free systems and human colon cell lines. Mol Nutr Food Res. 2010; 54:1734-43. https://doi. org/10.1002/mnfr.201000147 DOI:

Yen WJ, Wang BS, Chang LW, Duh PD. Antioxidant properties of roasted coffee residues. Agric Food Chem. 2005; 53:2658-63. DOI:

Yoshinari O, Takenake A, Igarashi K. Trigonelline ameliorates oxidative stress in type 2 diabetic Goto- Kakizaki rats. J Med Food. 2013; 16:34-41. https://doi. org/10.1089/jmf.2012.2311 DOI:

Daunde JA, Desai SS, Desai PJ, et al. Nano-scaling of Trigonelline Improves Antioxidative Status of hfdstz Induced Diabetic mice. Int J Res In Appl Sci Eng Technol. 2018; 6:2547-52.

Li GQ, Kam A, Wong KH, et al. Herbal Medicines for the Management of Diabetes. In: Ahmad SI, editor. Diabetes: An Old Disease, a New Insight, Advances in Experimental Medicine and Biology. New York, NY: Springer. 2013; pp. 396–413. https://doi. org/10.1007/978-1-4614-5441-0_28 DOI:

Osadebe PO, Odoh EU, Uzor PF. Natural Products as Potential Sources of Antidiabetic Drugs. Br J Pharm Res. 2014; 4(17):2075–95. BJPR/2014/8382 DOI:

EMA Assessment Report on Trigonella foenum-graecum L.; Semen. Available online: http://www.ema. europa. eu/docs/en_GB/document_library/Herbal_-_ HMPC_assessment_report/2011/04/WC500105228. pdf