Cell Biology and Toxicology

, Volume 23, Issue 6, pp 373–383 | Cite as

Fenugreek seed (Trigonella foenum graecum) polyphenols inhibit ethanol-induced collagen and lipid accumulation in rat liver

  • S. Kaviarasan
  • P. Viswanathan
  • C. V. AnuradhaEmail author
Original Article


Chronic alcoholism is associated with fatty liver and fibrosis characterized by collagen accumulation. Seeds of fenugreek, an annual herb, are reported to possess hepatoprotective activity. The study aims to investigate the effects of fenugreek seed polyphenol extract (FPEt) on liver lipids and collagen in experimental hepatotoxic rats. Hepatotoxicity was induced in male albino Wistar rats by administrating ethanol (6 g/kg per day) for 30 days. Control rats were given isocaloric glucose solution. FPEt was co-administered with ethanol at a dose of 200 mg/kg per day for the next 30 days. Silymarin was used as a positive control. Ethanol treatment caused increase in plasma and liver lipids, together with alterations in collagen content and properties. Administration of FPEt to alcohol-fed rats significantly improved lipid profile and reduced collagen content, crosslinking, aldehyde content and peroxidation. The effects were comparable with that of silymarin. FPEt administration had a positive influence on both lipid profile and on the quantitative and qualitative properties of collagen in alcoholic liver disease. The protective effect is presumably due to the bioactive phytochemicals in fenugreek seeds.


Collagen Ethanol Fenugreek seeds Lipids Polyphenols 



Duncan’s multiple range test


free fatty acids


fenugreek seed polyphenol extract


hematoxylin and eosin


high-density lipoprotein cholesterol


low-density lipoprotein cholesterol






very low-density lipoprotein cholesterol


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenum graecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fat Acids 1997;56:379–84.CrossRefGoogle Scholar
  2. Brandao DF, Ramalho LN, Ramalho FS, et al. Liver cirrhosis and hepatic stellate cells. Acta Cir Bras 2006;21:54–7.PubMedCrossRefGoogle Scholar
  3. Bunout D. Nutritional and metabolic effects of alcoholism: their relationship with alcoholic liver disease. Nutrition 1999;15(718):583–9.PubMedCrossRefGoogle Scholar
  4. Carson FL. Fixation, processing, instrumentation and routine staining. In: Carson FL, editor. Histechnology, a self-instructional text. Chicago: ASCP Press; 1990. p. 1–67.Google Scholar
  5. Carter EA, McCarron MJ, Alpert E, Isselbacher KJ. Lysyl-oxidase and collagenase in experimental acute and chronic liver injury. Gastroenterology 1982;82:526–34.PubMedGoogle Scholar
  6. Deulofeu R, Rubio M, Caballeria T, Jose M, Rodes J, Albert P. S-Adenosyl methionine prevents hepatic tocopherol depletion in CCl4-induced rats. Clin Sci 2002;97:315–20.Google Scholar
  7. Dixit P, Ghaskadbi S, Mohan H, Devasagayam TPA. Antioxidant properties of germinated fenugreek seeds. Phytother Res 2005;19:977–83.PubMedCrossRefGoogle Scholar
  8. Falholt K, Falholt W, Lund B. An easy colorimetric method for routine determination of free fatty acids in plasma. Clin Chim Acta 1973;46:105–11.PubMedCrossRefGoogle Scholar
  9. Folch J, Lees M, Stanely GHS. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957;126:496–509.Google Scholar
  10. Foster CS, Dunn O. Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method. Clin Chem 1973;19:338–40.PubMedGoogle Scholar
  11. Fujimori E. Cross-linking and fluorescence changes of collagen by glycation and oxidation. Biochim Biophys Acta 1995;998:105–10.Google Scholar
  12. Gupta R, Nair S. Antioxidant flavonoids in common Indian diet. South Asian J Prev Cardiol 1999;3:83–94.Google Scholar
  13. Iqbal M, Sharma SD, Rezaza Deh H, Abdullia M, Hassan N, Athar M. Glutathione metabolizing enzymes and oxidative stress in Fe-NTA mediated liver injury. Redox Rep 1996;2:385–91.Google Scholar
  14. Kang LP, Hong QL, Zhang JP, et al. Effect of genistein and quercetin on proliferation, collagen synthesis and type I procollagen mRNA levels of rat hepatic stellate cells. Acta Pharmacol Sin 2001;22:793–6.PubMedGoogle Scholar
  15. Kaviarasan S, Vijayalakshmi K, Anuradha CV. Polyphenol-rich extract of fenugreek seeds protect erythrocytes from oxidative damage. Plant Food Hum Nutr 2004;59:143–7.CrossRefGoogle Scholar
  16. Kaviarasan S, Ramamurty N, Gunasekaran P, Varalakshmi E, Anuradha CV. Fenugreek seed extract prevents ethanol-induced toxicity and apoptosis in Chang liver cells. Alcohol Alcohol 2006;41:267–3.PubMedGoogle Scholar
  17. Kerai MDJ, Waterfiled CJ, Kenyon SH, Asker DS, Timbrell JA. Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats. Alcohol Alcohol 1999;34:529–41.PubMedGoogle Scholar
  18. Khosla P, Gupta DD, Nagpal RK. Effect of Trigonella foenum graecum (fenugreek) on serum lipids in normal and diabetic rats. Int J Pharmacol 1995;27:89–93.Google Scholar
  19. Lee KS, Buck M, Houglum K, Chojkier M. Activation of HSC by TGF-alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest 1995;96:2461–8.PubMedGoogle Scholar
  20. Liu X, Wang W, Hu H, et al. Smad3 specific inhibitor, naringenin, decreases the expression of extracellular matrix induced by TGF-beta1 in cultured rat hepatic stellate cells. Pharm Res 2006;23:82–9.PubMedCrossRefGoogle Scholar
  21. Lowry OH, Rosebrough MJ, Farr L, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75.PubMedGoogle Scholar
  22. Mang J, Sakata N, Takebayashi S. AGE of the Mailard reaction in aortic pepsin-insoluble and pepsin soluble collagen from diabetic rats. Diabetes 1996;45:1037–43.CrossRefGoogle Scholar
  23. Mao YQ, Liu XJ, Jiang Y, Wu HB. Effect of quercetin on the signal pathway of TGFbeta1 in activated hepatic stellate cells. Sichuan Da Xue Xue Bao Yi Xue Ban 2004;35:802–5.PubMedGoogle Scholar
  24. Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev 2000;52:673–751.PubMedGoogle Scholar
  25. Miller EJ, Rhodes RK. Preparation and characterization of different types of collagen. Methods Enzymol 1982;82:33–64.PubMedGoogle Scholar
  26. Monnier VM, Viswanath V, Frank KE, Elmels CA, Dauchot P, Kohn RR. Relation between complications of type I diabetes mellitus and collagen-linked fluorescence. New Engl J Med 1986;314:403–8.PubMedCrossRefGoogle Scholar
  27. Nanji AA. Dietary fatty acids and alcoholic liver disease: pathogenic mechanisms. Alcohol Clin Exp Res 1998;22:747–8.CrossRefGoogle Scholar
  28. Parker JG, Awerbach W, Goldbag DM. Effect of alcohol on lipoprotein metabolism. Enzyme 1996;43:47–55.Google Scholar
  29. Parola M, Pinzani M, Casini A, et al. Induction of procollagen type I gene expression and synthesis in human hepatic stellate cells by 4-hydroxy 2,3-nonenal and other 4-hydroxy-2,3-alkenals is related to their molecular structure. Biochem Biophys Res Commun 1996;222:261.PubMedCrossRefGoogle Scholar
  30. Paz MA, Lent RW, Faris B, Franzblau C, Blumenfeld OO, Gallop PM. Aldehydes in native and denatured calf skin tropocollagen. Biochem Biophys Res Commun 1969;34:221–9.PubMedCrossRefGoogle Scholar
  31. Purohit V, Brenner DA. Mechanisms of alcohol-induced hepatic fibrosis: a summary of the Ron Thurman symposium. Hepatology 2006;43:872–8.PubMedCrossRefGoogle Scholar
  32. Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant derived polyphenolic flavonoids. Free Radic Res 1995;22:375–83.PubMedCrossRefGoogle Scholar
  33. Rudney H, Sexton RC. Regulation of cholesterol biosysnthesis. Annu Rev Nutr 1986;6:245–72.PubMedCrossRefGoogle Scholar
  34. Sauvaire Y, Ribes G, Baccou J, Loubatieres-Mariani M. Implication of steroid saponins and sapogenins in the hypocholesterolemic effect of fenugreek. Lipids 1991;26:191–7.PubMedCrossRefGoogle Scholar
  35. Shang M, Cai S, Han J, et al. Studies on flavonoids from fenugreek (Trigonella foenum graecum L). Zhongguo Zhong Yao Za Zhi 1998a;23:614–6.Google Scholar
  36. Shang M, Cai S, Wang X. Analysis of amino acids in Trigonella foenum graecum seeds. Zhong Yao Cai 1998b;21:188–90.Google Scholar
  37. Sharma RD. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr Res 1986;6:1353–64.CrossRefGoogle Scholar
  38. Sharma RD, Raghuram TC, Dayasagar Rao V. Hypolipidaemic effect of fenugreek seeds. A clinical study. Phytother Res 1991;3:145–7.CrossRefGoogle Scholar
  39. Sharma RD, Sarkar A, Hazra DK. Hypolipidaemic effects of fenugreek seeds: a chronic study in non-insulin dependent diabetic patient. Phytother Res 1996;10:332–4.CrossRefGoogle Scholar
  40. Singleton SL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic–phosphotungstic acid reagents. Am J Enol Vitic 1965;16:144–58.Google Scholar
  41. Stark A, 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;69:277–87.PubMedCrossRefGoogle Scholar
  42. Thirunavukkarasu V, Anuradha CV, Viswanathan P. Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity. Phytother Res 2003;17:737–43.PubMedCrossRefGoogle Scholar
  43. Woessner JF Jr. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys 1961;93:440–7.PubMedCrossRefGoogle Scholar
  44. Xia J, Allenbrand B, Sun GY. Dietary supplementation of grape polyphenols and chronic ethanol administration on LDL oxidation and platelet function in rats. Life Sci 1998;63:383–90.PubMedCrossRefGoogle Scholar
  45. Zilversmit DB, Davis AK. Microdetermination of plasma phospholipids by trichloroacetic acid precipitation. J Lab Clin Invest 1950;35:155–60.Google Scholar
  46. Zlatki A, Zak B, Boyle AJ. A new method for the direct determination of serum cholesterol. J Lab Clin Med 1953;45:486–92.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • S. Kaviarasan
    • 1
  • P. Viswanathan
    • 2
  • C. V. Anuradha
    • 1
    Email author
  1. 1.Department of Biochemistry, Faculty of ScienceAnnamalai UniversityAnnamalai NagarIndia
  2. 2.Department of Pathology, Faculty of Medicine, RMMC&HAnnamalai UniversityAnnamalai NagarIndia

Personalised recommendations