Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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Toxicity studies on Trigonella foenum-graecum L. seeds used in spices and as a traditional remedy for diabetes

  • Al-Ashban, R.M. (Central Laboratory for Drug Analysis, Ministry of Health and Saudi Food and Drug Authority Joint Venture, King Saud Medical Complex) ;
  • Abou-Shaaban, R.R. (Central Laboratory for Drug Analysis, Ministry of Health and Saudi Food and Drug Authority Joint Venture, King Saud Medical Complex) ;
  • Shah, A.H. (Central Laboratory for Drug Analysis, Ministry of Health and Saudi Food and Drug Authority Joint Venture, King Saud Medical Complex)
  • Received : 2009.03.04
  • Accepted : 2010.04.06
  • Published : 2010.06.30
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Abstract

Acute (24 h) and chronic (90 days) oral toxicity studies on the ethanol extract of Trigonella foenumgraecum Leguminosae (L.) seeds were carried out. Acute dosages were 0.5, 1.0 and 3 g/kg while chronic dosage was 100 mg/kg per day of the extract. All morphological, biochemical, haematological and spermatogenic changes, in addition to mortality, body weight changes and any change in vital organs were recorded. Histopathological investigations were done on vital organs. Growth arrest in the treated animals was observed. The treated mice gained no significant weight during chronic treatment while there was a significant gain in body weight of the control group mice. Biochemical studies revealed a significant decrease in blood sugar levels of fenugreek treatment groups while haematological parameters remained comparable to the control. In the treatment, male group there was a significant decrease in weight of testes as compared to the control. There was a marginal weight gain in kidney weight of mice after chronic treatment as compared to the control. Fenugreek chronic treatment caused a highly significant spermatotoxic effects in male mice.

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References

  1. Abdel-Barry JA, Abdel-Hassan IA, Al-Hakiem MH. (1997) Hypoglycemic and antihyperglycemic effects of Trigonella foenum-graecum leaf in normal and alloxan induced diabetic rats. J. Ethnopharmacol. 58, 149-155. https://doi.org/10.1016/S0378-8741(97)00101-3
  2. Adamska M, Lutomski J. (1971) C-Glycoside flavonesin the seeds of Trigonella foenum- graecum. Planta Med. 20, 224-229. https://doi.org/10.1055/s-0028-1099697
  3. Ahsan SK, Tariq M, Ageel AM, Al-Yahya MA, Shah AH. (1989) Effect of Trigonella foenum-graecum and Ammi majus on the inhibition of Calcium oxalateurolethiasis in rats. J. Ethnopharmacol. 26, 249-253. https://doi.org/10.1016/0378-8741(89)90097-4
  4. Ajabnoor MA, Tilmisany AK. (1998) Effect of Trigonella foenum-graecum on blood glucose levels in normal and alloxan diabetic mice. J. Ethnopharmacol.22, 45-49.
  5. Al-Ashban RM, Barrett DA, Shah AH. (2005) Effects of chronic treatment with ethanolic extract of Teucrium polium in mice”. J. Herb Spices Med. Plants 11, 27-36.
  6. Al-Habori M, Raman A. (1998) Antidiabetic and hypocholesterolaemic effects of Fenugreek. Phytother. Res. 12, 233–242.
  7. Al-Habori M, Raman A, Lawrence MJ, Skett P. (2001) In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A. Int. J. Exp. Diabetes Res. 2, 91-99. https://doi.org/10.1155/EDR.2001.91
  8. Ali L, Azad-Khan AK, Hassan Z, Mosihuzzaman M, Nahar N, Nasreen T, Nur-e-Alam M, Rokeya B. (1995). Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Planta Med. 61, 358-360. https://doi.org/10.1055/s-2006-958100
  9. Amin A, Alkaabi A, Al-Falasi S, Daoud SA. (2005) Chemopreventive activities of Trigonella foenum graecum (Fenugreek) against breast cancer. Cell Biol. Int. 29, 687-694. https://doi.org/10.1016/j.cellbi.2005.04.004
  10. Barnes J, Anderson LA, Phillipson JD. (2002) Herbal Medicines – A Guide for Healthcare Professionals. 2nd ed., pp. 209-210, Pharmaceutical Press, London, UK.
  11. Bin-Hafeez B, Haque R, Parvez S, Pandey S, Sayeed I, Raisuddin S. (2003) Immunomodulatory effects of fenugreek (Trigonella foenum-graecum L.) extract in mice. Inter. Immunopharmacol. 3, 257-265. https://doi.org/10.1016/S1567-5769(02)00292-8
  12. Brinkworth MH, Anderson D, Gangolli SD. (1987) Correlation of raised level of abnormal sperm morphology with electrophoretic sperm protein changes. Mut. Res. 2, 306-309.
  13. Chopra RN, Nayar SL, Chopra IC. (1956) Glossary of Indian Medicinal Plants. pp. 248-249, Council of Scientific & Industrial Research, New Delhi, India.
  14. Dawidar AM, Saleh AA, El-Motei SL. (1973) Steroid sapogenin constituents of fenugreek seeds. Planta Med. 24, 367-370. https://doi.org/10.1055/s-0028-1099510
  15. DerMarderosian A, Beutler JA. (2002) The Review of Natural Products. The Most Complete Source of Natural Product Information, pp. 253-254 Published by Facts and Comparisons, St. Louis, Missouri, USA.
  16. Dixit PP, Devasagayam TP, Ghaskadbi S. (2008) Formulated antidiabetic preparation Syndrex has a strong antioxidant activity. Eur. J. Pharmacol. 581,216-225. https://doi.org/10.1016/j.ejphar.2007.11.052
  17. Dixit P, Ghaskadbi S, Mohan H, Devasagayam TP. (2005) Antioxidant properties of germinated fenugreek seeds. Phytother. Res. 19, 977-983. https://doi.org/10.1002/ptr.1769
  18. Duke JA. (2001) Handbook of Medicinal Herbs. P. 490, CRC Press LLC, Boca Raton, Florida, USA.
  19. Dweck AC. (1997) African fragranced plants. Cosmet. Toiletries 112, 47-54.
  20. Faeste CK, Namork E, Lindvik H. (2009) Allergenicity and antigenicity of fenugreek (Trigonella foenumgraecum) proteins in food. J. Aller. Clin. Immunol.123, 187-194. https://doi.org/10.1016/j.jaci.2008.09.012
  21. Flamming AM, Cifone MA, Erexson GL, Stankowski LF Jr. (2004) Genotoxicity testing of a fenugreek extract. Food Chem. Toxicol., 42, 1769-1775. https://doi.org/10.1016/j.fct.2004.07.003
  22. Ghafghazi T, Sheriat HS, Dastmalchi T, Barnett RC. (1977) Antagonism of cadmium and alloxaninduced hyperglycemia in rats by Trigonella foenumgraecum. Pahlavi Med. J. 8,14-25.
  23. Gruenwald J, Brendler T, Jaenicke C. (2000) PDR for Herbal Medicines. pp. 304-305, Medical Economics Company Inc. Montvale. New Jersey, USA.
  24. Gupta RK, Jain DC, Thakur RS. (1986) Minor steroidal sapogenins from fenugreek seeds, Trigonella foenumgraecum. J. Nat. Prod. 49, 1153. https://doi.org/10.1021/np50048a043
  25. Haddad PS, Depot M, Settaf A, Cherrah Y. (2001) Use of Antidiabetic Plants in Morocco and Quebec. Diabetes Care 24, 608-609. https://doi.org/10.2337/diacare.24.3.608
  26. Haefele C, Bonfils C, Sauvaire Y. (1997) Characterization of a dioxygenase from Trigonella foenum-graecum involved in 4-hydroxyisoleucine biosynthesis. Phytochemistry 44, 563-566. https://doi.org/10.1016/S0031-9422(96)00620-6
  27. Haeri MR, Izaddoost M, Ardekani MR, Nobar MR, White KN. (2009) The effect of fenugreek 4-hydroxyisoleucine on liver function biomarkers and glucose in diabetic and fructose-fed rats. Phytother. Res. 23, 61-64. https://doi.org/10.1002/ptr.2557
  28. Hannan JM, Ali L, Rokeya B, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YH. (2007). Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. Brit. J. Nutr. 97, 514-521. https://doi.org/10.1017/S0007114507657869
  29. Haouala R, Hawala S, El-Ayeb A, Khanfir R, Doughanmi N. (2008) Aqueous and organic extracts of Trigonella foenum-graecum L. inhibit the mycelia growth of fungi. J. Environ. Sci. China 20, 1453-1457. https://doi.org/10.1016/S1001-0742(08)62548-6
  30. Hibasami H, Moteki H, Ishikawa K, Katsuzaki H, Imai K, Yoshioka K, Ishii Y, Komiya T. (2003) Protodioscin isolated from fenugreek (Trigonella foenum-graecum 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. Inter. J. Mol. Med.11, 23-26.
  31. Hunt LM, Arar NH, Akana LL. (2000) Herbs, prayer, and insulin: use of medical and alternative treatments by a group of Mexican-American diabetic patients.J. Fam. Pract. 49, 216–223.
  32. Hussein FTK. (1985) Medicinal Plants in Libya. P. 798, Arab Encyclopedia House, Beirut, Lebanon.
  33. Karawya MS, Wassel GM, Baghdadi HH, Ammar NM. (1980) Mucilagenous contents of certain Egyptian plants. Planta Med. 38, 73-78. https://doi.org/10.1055/s-2008-1074840
  34. Kassem A, Al-Aghbari A, Al-Habori M, Al-Mamary M. (2006) Evaluation of the potential antifertility effect of fenugreek seeds in male and female rabbits.Contraception 73, 301-306. https://doi.org/10.1016/j.contraception.2005.08.020
  35. Kaviarasan S, Sundarapandiyan R, Anuradha CV. (2008) Protective action of fenugreek (Trigonella foenum graecum) seed polyphenols against alcoholinduced protein and lipid damage in rat liver. Cell Biol. Toxicol. 24, 391-400. https://doi.org/10.1007/s10565-007-9050-x
  36. Kaviarasan S, Viswanathan P, Anuradha CV. (2007). Fenugreek seed (Trigonella foenum graecum) polyphenols inhibit ethanol-induced collagen and lipid accumulation in rat liver. Cell Biol. Toxicol. 24, 71-76.
  37. Khater HF, Shalaby AA. (2008) Potential of biologically active plant oils to control masquito larvae (Culex pipiens, Diptera: Culicidae) from an Egyptian locality. Rev. Inst. Med. Trop. S. Paulo 50, 107-112. https://doi.org/10.1590/S0036-46652008000200008
  38. Khosla P, Gupta DD, Nagpal RK. (1995) Effect of Trigonella foenum graecum (Fenugreek) on blood glucose in normal and diabetic rats. Indian J. Physiol. Pharmacol. 39, 173-174.
  39. Khurana SK, Krishnamoorthy V, Parmar VS, Sanduja R, Chawla HL. (1982) 3,4,7-methyl-coumarin from Trigonella foenum-gracecum stems. Phytochemistry 21,2145-2147. https://doi.org/10.1016/0031-9422(82)83074-4
  40. Malviya KG, Babhulkar MW, Mali PY, Rangari VD. (2010) Evaluation of anti-inflammatory potential of Trigonella foenum-graecum (Fenugreek) seed extractby using carrageenan induced rat paw edema. Drug Invention Today 2, 109-111.
  41. Marles RJ, Farnsworth NR. (1995) Antidiabetic plants and their active constituents. Phytomed. 2, 137–189.
  42. Mishkinsky J, Joseph B, Sulman F. (1967) Hypoglycemic effect of trigonelline. Lancet 2, 1311-1312.
  43. Mondal DK, Yousuf BM, Banu LA, Ferdousi R, Khalil M. and Shamim KM. (2004). Effect of fenugreek seeds on the fasting blood glucose level in thestreptozotocin induced diabetic rats. Mymensingh Med. J. 13, 161-164.
  44. Murakami T, Kishi A, Matsuda H, Yoshikawa M. (2000) Medicinal foodstuffs. XVII. Fenugreek seed -3: Structures of new furostanol-type steroid saponins,trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa, from the seeds of Egyptian Trigonella foenum-graecum L. Chem. Pharm. Bull. (Tokyo), 48, 994-1000. https://doi.org/10.1248/cpb.48.994
  45. Muralidhara N, Narasimhamurthy K, Viswanatha S., Ramesh BS. (1999). Acute and subchronic toxicity assessment of debitterized fenugreek powder in the mouse and rat. Food. Chem. Toxicol. 37, 831-838. https://doi.org/10.1016/S0278-6915(99)00076-9
  46. Nakhla HB, Mohamed OS, Abu IM, Fatuh AL, Adam SE. (1991) The effect of Trigonella foenum graecum (fenugreek) crude saponins on Hisex-type chicks.Vet. Hum. Toxicol. 33, 561-564.
  47. Narender T, Puri A, Shweta KT, Saxena R, Bhatia G, Chandra R. (2006) 4-hydroxyisoleucine an unusual amino acid as antidyslipidemic and antihyperglycemic agent. Bioorg. Med. Chem. Lett. (15-16), 293-296.
  48. Otoom SA, Al-Saifi SA, Kerem ZK, Alkofahi A. (2006) The use of medicinal herbs by diabetic Jordanian patients. J. Herb Pharmacother. 6, 31-41. https://doi.org/10.1300/J157v06n02_03
  49. Palaniswamy M, Pradeep BV, Sathya R, Angayarkanni J. (2008) In vitro anti-plasmodial activity of Trinonella foenum-graecum L. Evid. Based Complement. Alternat. Med., May 2. PMID: 18955334.
  50. Pandian RS, Anuradha CV, Viswanathan P. (2002) Gastroprotective effect of fenugreek seeds (Trigonella foenum graecum) on experimental gastric ulcer inrats. J. Ethnopharmacol. 81, 393-397. https://doi.org/10.1016/S0378-8741(02)00117-4
  51. Pasich B, Terminska K, Beblot D. (1983) Diosgenin and yamogenin in domestic Semen foenugraeci. Herba Polonica 29, 203-209.
  52. Patil SP, Niphadkar PV, Bapat MM. (1997) Allergy to fenugreek (Trigonella foenum graecum). Ann. Allergy Asthma Immunol. 78, 297-300. https://doi.org/10.1016/S1081-1206(10)63185-7
  53. Puri D, Prabhu KM, Murthy PS. (2002) Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds. Ind. J. Physiol. Pharmacol. 46, 457-462.
  54. Qureshi S, Al-Yahya MA, Mossa JS, Tariq M, Ageel AM, Shah AH. (1990) Preliminary toxicity studies on ethanol extract of the aerial parts of Artemisia abyssinica and A. inculta. J. Ethnopharmacol. 28, 157-162. https://doi.org/10.1016/0378-8741(90)90025-O
  55. Raju J, Gupta D, Rao AR, Yadava PK, Baquer NZ. (2001). Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxandiabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. Mol. Cell Biochem. 224, 45-51. https://doi.org/10.1023/A:1011974630828
  56. Raju J, Patlolla JM, Swamy MV, Rao CV. (2004). 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. 13, 1392-1398.
  57. Ribes G, Costa CD, Mariani LMM, Sauvaire Y, Baccou JC. (1987) Hypocholesterolemic and hypotriglyceridmeic effects of sub fractions of fenugreek seeds in alloxan diabetic dogs. Phytotherapeutic Res. 1, 8-43.
  58. Rohini RM, Nayeem N, Das AK. (2009) Diuretic effect of Trigonella foenum-graecum seed extracts. Internet J. Alternat. Med. 6,ISSN 1540-2584.
  59. Satheeshkumar N, Mukherjee PK, Bhadra S, Saha BP. (2010) Acetycholinesterase enzyme inhibitory potential of standardized extract of Trigonella foenum-graecum L. and its constituents. Phytomedicine 17, 292-295. https://doi.org/10.1016/j.phymed.2009.06.006
  60. Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, Gross R, Roye M, Leconte A, Gomis R, Ribes G. (1998). 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 47, 206-210. https://doi.org/10.2337/diabetes.47.2.206
  61. Shlosberg A, Egyed MN. (1983) Examples of poisonous plants in Israel of importance to animals and man. Arch. Toxicol. Suppl. 6, 194-196.
  62. Shabbeer S, Sobolewski M, Anchoori RK, Kachhan S, Davidson N, Carducci MA, Khan SR. (2009) Fenugreek: A naturally occurring edible spice as an anticancer agent. Cancer Biol. Ther. 8, 8.
  63. Shah AH, Al-Shareef AH, Qureshi S, Ageel AM. (1998) Toxicity studies on some common spices: Cinnamomum zylanicum and Piper longum. Plant Fds. Used in Human Nutr. 52, 231-241. https://doi.org/10.1023/A:1008088323164
  64. Shah AH, Qureshi S, Tariq M, Ageel AM. (1989) Toxicity studies on six plants used in Traditional Arab System of Medicine. Phytother. Res. 3, 25-29. https://doi.org/10.1002/ptr.2650030107
  65. Shani J, Goldschmidt A, Joseph B, Ahronson Z, Sulma FG. (1974). Hypoglycemic effect of Trigonella foenum graecum and lupinus termis (Leguminosae) seeds and their major alkaloid in alloxan diabetic and normal rats. Arch. Inter. Pharmacody. Therapeut. 210, 27-36.
  66. Shim SH, Lee EJ, Kim JS, Kang SS, Ha H, Lee HY, Kim C, Lee JH, Son KH. (2008). Rat growth-hormone release stimulators from fenugreek seeds. Chem. Biodivers 9, 1753-1761.
  67. Srichamroen A, Thomson AB, Field CJ, Basu TK. (2009) In vitro intestinal glucose uptake is inhibited by galactomannan from Canadian fenugreek seed(Trigonella foenum-graecum L) in genetically lean and obsess rats. Nutr. Res. 29, 49-54. https://doi.org/10.1016/j.nutres.2008.11.002
  68. Sur P, Das M, Gomes A, Vedasiromoni JR, Sahu NP, Banerjee S, Sharma RM, Ganguly DK. (2001) Trigonella foenum graecum (fenugreek) seed extract as anantineoplastic agent. Phytother. Res. 15, 257-259. https://doi.org/10.1002/ptr.718
  69. Tahiliani P, Kar A. (2003) Mitigation of thyroxine induced hyperglycemia by two plant extracts. Phytotherapy Res. 17, 294-296. https://doi.org/10.1002/ptr.1121
  70. Taylor WG, Zaman MS, Mir Z, Mir PS, Acharya SN, Mears GJ, Elder JL. (1997) Analysis of steroidal sapogenins from amber fenugreek (Trigonella foenumgraecum) by capillary gas chromatography and combined gas chromatography-mass spectrometry. J. Agric. Food Chem. 45, 753-759. https://doi.org/10.1021/jf960200n
  71. Thirunavukkarasu V, Anuradha CV, Viswanathan P. (2003) Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity.Phytother. Res. 17, 737-743. https://doi.org/10.1002/ptr.1198
  72. Valette G, Sauvaire Y, Baccou JC, Ribes G. (1984) Hypocholesterolaemic effect of fenugreek seeds in dogs. Atherosclerosis 50, 105-111. https://doi.org/10.1016/0021-9150(84)90012-1
  73. Vats V, Yadav SP, Grover JK. (2003) Effect of T. foenum-graecum on glycogen content of tissues and the key enzymes of carbohydrate metabolism. J. thnopharmacol. 85, 237-242. https://doi.org/10.1016/S0378-8741(03)00022-9
  74. Vyas S, Agrawal RP, Solanki P, Trivedi P. (2008) Analgesic and anti-inflammatory activities of Trigonella foenum-graecum (seed) extract. Acta Pol. Pharm. 65, 473-476.
  75. W.H.O. Scientific Group. (1967). Principles for Preclinical Testing of Drugs Safety. Technical Report Series, 341, pp. 9-11. World Health Organization,Geneva, Switzerland.
  76. Wyrobek AJ, Gordon LA, Burkhart JG, Francis MW, Kappa Jr. RW, Letz G, Malling HV, Topham JC, Whorton MD. (1983) An evaluation of the mouse sperm morphology test and other sperm tests in non-human mammals. Mut. Res. 115, 1-64. https://doi.org/10.1016/0165-1110(83)90014-3
  77. Wyrobek AJ, Bruce WR. (1975) Chemical induction of sperm abnormalities in mice. Proc. Nat. Acad. Sci. USA, 72, 4425–4429.
  78. Xu Y, Chen J, Mao H, Liu D. (1992) X-ray fluorescence spectrometric determination of phospholipids in semen Trigonella foenum-graecum. Fenxi-Huaxue 20, 219-222.
  79. Yang WX, Huang HY, Wang YJ, Jia ZY, Li LL. (2005) Study on chemical constituents in total saponin from Trigonella foenum-graecum. Zhongguo Zhong Yao Za Zhi. 30, 1428-1430.
  80. Yoshikawa M, Murakami T, Komatsu H, Murakami N, Yamahara J, Matsuda H. (1997) 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) 45, 81-87. https://doi.org/10.1248/cpb.45.81
  81. Zhao HQ, Qu Y, Wang XY, Lu XY, Zhang XH, Hattori M. (2003) Determination of trigonelline by HPLC and study on its pharmacokinetics. Yao Xue Xue Bao 38, 279-328.

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