Effects of Silybum marianum Extract on High-Fat Diet Induced Metabolic Disorders in Rats

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Abstract

Silybum marianum extract (SME) has been used for centuries as a natural remedy for diseases of liver and biliary tract. Lately, it has been promoted as a nutritional supplement for beneficial effects on some risk factors of diabetes and hyperlipidemia. In this study we aimed to determine the effects of SME on high-fat diet (HFD) induced metabolic disorders. Male Sprague Dawley rats were fed HFD for 11 weeks to induce obesity. SME was given to animals for two different durations, for 11 weeks or for 7 weeks. The results showed significant increase in plasma transaminases, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), leptin, high sensitive C-reactive protein (hsCRP), glucose and insulin along with significant increase in body mass index (BMI) and liver weights in rats fed the HFD diet compared to rats fed with standard rat diet. SME supplementation for different durations raised improvement in the HFD-induced metabolic disorders such as insulin resistance, hyperlipidemia and hepatopathy at different degrees. Our study concludes that SME can be well considered as an effective supplement to improve insulin and leptin sensitivity and hyperlipidemia and to suppress body weight gain.

1. Abdul S., Hussain R., Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J. Med. Food, 2007, 10, 543–547.

2. Abenavoli L., Capasso R., Milic N., Capasso F., Milk thistle in liver diseases: past, present, future. Phytother. Res., 2010, 24, 1423–1432.

3. Amasyalı E., Kılıçlı F., Say R., Uygungelen B., Acıbucu F., The relation between non-alcoholic fatty liver disease and hs-CRP levels in patients with metabolic syndrome. Cumhuriyet Med. J., 2010, 32, 26–33 (in Turkish).

4. Barness L.A., Opitz J.M., Gilbert-Barness E., Obesity: genetic, molecular, and environmental aspects. Am. J. Med. Genet., 2007, 143A, 3016–3034.

5. Baquer N.Z., Glucose over utilization and under utilization in diabetes and effects of antidiabetic compounds. Anales de la Real Academia de Farmacia, 1998, 64, 147–180.

6. Bergmeyer H.U., Horder M., Moss D.W., Provisional recommendations on IFCC methods for the measurement of catalytic concentrations of enzymes. Part 3. Revised IFCC method of aspartate aminotransferase (L-Aspartate:2-oxoglutarate amino-transferase, EC 2.6.1.1) Clin. Chem., 1978, 24/4, 720–721.

7. BrahmaNaidu P., Nemani H., Meriga B., Mehar S.K., Potana S., Ramgopalrao S., Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats. Chem. Biol. Inter., 2014, 221, 42–51.

8. Bulló M., Casas-Agustench P., Amigó-Correig P., Aranceta J., Salas-Salvadó J., Inflammation, obesity and comorbidities: the role of diet. Publ. Health Nutr., 2007, 10, 1164–1172.

9. Chen I.S., Chen Y.C., Chou C.H., Chuang R.F., Sheend L.Y., Chiub C.H., Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis. J. Sci. Food Agric., 2012, 92, 1441–1447.

10. Crocenzi F.A., Pellegrino J.M., Pozzi E.J.S., Mottino A.D., Garay E.A.R., Roma M.G., Effect of silymarin on biliary bile salt secretion in the rat. Biochem. Pharmacol., 2000, 59, 1015–1022.

11. Dehmlow C., Erhard J., de Groot ., Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology, 1996, 23, 749–754.

12. El Mesallamy H.O., Metwally N.S., Soliman M.S., Ahmed K.A., Abdel Moaty M.M., The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. Cancer Cell Int., 2011, 11, 38.

13. Falasca K., Ucciferri C., Mancino P., Vitacolonna E., Tullio D., Pizzigallo E., Conti P., Vecchiet J., Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection. J. Med. Virol., 2008, 80, 1900–1906.

14. Flanagan A.M., Brown J.L., Santiago C.A., Aad P.Y., Spicer J.L., Spicer M.T., High-fat diets promote insulin resistance through cytokine gene expression in growing female rats. J. Nutr. Biochem., 2008, 19, 505–513.

15. Fried M., Hainer V., Basdevant A., Buchwald H., Dietel M., Finer N., Greve J.W., Horber F., Mathus-Vliegen E., Scopinaro N., Steffen R., Weiner R., Widhalm K., Interdisciplinary European guidelines on surgery for severe obesity. Rozhl. Chir., 2008, 87, 468–476.

16. Friedman J.M., Halaas J.L., Leptin and the regulation of body weight in mammals. Nature, 1998, 395, 763–770.

17. Galletti F., Barbato A., Versiero M., Iacone R., Russo O., Barba G., Siani A., Cappuccio FP., Farinaro E., della Valle E., Strazzullo P., Circulating leptin levels predict the development of metabolic syndrome in middle-aged men: an 8-year follow-up study. J. Hypertens., 2007, 25, 1671–1675.

18. Ghaffari A.R., Noshad H., Ostadi A., Ghojazadeh M., Asadi P., The effects of milk thistle on hepatic fibrosis due to methotrexate in rat. Hepat. Mon., 2011, 11, 464–468.

19. Gopalakrishnan R., Sundaram J., Sattu K., Pandi A., Thiruvengadam D., Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis. Invest. New Drug., 2009, 27, 233–240.

20. Grundy S.M., Obesity, metabolic syndrome and cardiovascular disease. J. Clin. Endo. Metab., 2004, 89, 2595–2600.

21. Haddad Y., Vallerand D., Brault A., Haddad P.S., Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis. Evidence Based Compl. Alt. Med., 2011, 2011, hep164.

22. Hamza N., Berke B., Cheze C., Agli A.N., Robinson P., Gin H., Moore N., Prevention of type 2 diabetes induced by high fat diet in the C57BL/6J mouse by two medicinal plants used in traditional treatment of diabetes in the east of Algeria. J. Ethnopharmacol., 2010, 128, 513–518.

23. Kim J.Y., Nolte L.A., Hansen P.A., Han D.H., Ferguson K., Thompson P.A., Holloszy J.O., High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2000, 279, R2057–R2065.

24. Kren V., Walterová D., Silybin and silymarin: new effects and applications. Biomed. Pap., 2005, 149, 29–41.

25. Lahiri-Chatterjee M., Katiyar S.K., Mohan R.R., Agarwal R., A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the sencar mouse skin tumorigenesis model. Can. Res., 1999, 59, 622–632.

26. Lim D.W., Kim Y.T., Jang Y.J., Kim Y.E., Han D., Anti-obesity effect of Artemisia capillaris extracts in high-fat diet-induced obese rats. Molecules, 2013, 18, 9241–9252.

27. Li Volti G., Salomone S., Sorrenti V., Mangiameli A., Urso V., Siarkos I., Galvano F., Salamone F., Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice. Cardiovasc. Diabet., 2011, 10, 62–70.

28. Maguire T., Haslam D., The Obesity Epidemic and its Management. 2010, Pharmaceutical Press, London, pp. 264–267.

29. Marović D., Elevated body mass index fatty liver. Srp. Arh. Celok. Lek., 2008, 136, 122–125.

30. Mao Z.M., Song H.Y., Yang L.L., Liu T., Li D.F., Zheng P.Y., Liu P., Ji G., Effects of the mixture of Swertia pseudochinensis Hara and Silybum marianum Gaertn extracts on CCl(4)-induced liver injury in rats with non-alcoholic fatty liver disease. Zhong Xi Yi Jie He Xue Bao, 2012, 10, 193–199.

31. Mashmoul M., Azlan A., Yusof B.N.M., Khaza’ai H., Mohtarrudin N., Boroushaki M.T., Effects of saffron extract and crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet. J. Funct. Foods, 2014, 8, 180–187.

32. Montani J.P., Carroll J.F., Dwyer T.M., Antic V., Yang Z., Dulloo A.G., Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Int. J. Obes., 2004, 28, 58–65.

33. Novelli E.L., Diniz Y.S., Galhardi C.M., Ebaid G.M., Rodrigues H.G., Mani F., Fernandes A.A., Cicogna A.C., Novelli Filho J.L., Anthropometrical parameters and markers of obesity in rats. Lab. Anim., 2007, 41, 111–119.

34. Pittler M.H., Schmidt K., Ernst E., Adverse events of herbal food supplements for body weight reduction: systematic review. Obes. Rev., 2005, 6, 93–111.

35. Poirier P., Giles T.D., Bray G.A., Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation, 2006,113, 898–918.

36. Pradhan S.C., Girish C., Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J. Med. Res., 2006, 124, 491–504.

37. Prakash P., Singh V., Jain M., Rana M., Khanna V., Barthwal M.K., Dikshit M., Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat. Eur. J. Pharmacol., 2014, 727, 15–28.

38. Raja S., Ahmed K., Kumar V., Mukherjee K., Bandyopadhyay A., Mukherjee P., Antioxidant effect of Cytisus scorparius against carbon tetrachloride treated liver injury in rat. J. Ethnopharmacol., 2007, 109, 41–47.

39. Ramakrishnan G., Raghavendran H.R., Vinodhkumar R., Devaki T., Suppression of nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem. Biol. Interact., 2006, 161, 104–114.

40. Rautela G.S., Hall R.G., Jr Bekiesz C.L., Wermus G.R., A kinetic method for the rapid and automatic measurement of triglycerides in biological fluids. Clin. Chem., 1974, 20, 857–862.

41. Rautela G.S., Liedtke R.J., Automated enzymic measurement of total cholesterol in serum. Clin. Chem., 1978, 24, 108–114.

42. Salamone F., Galvano F., Marino A., Paternostro C., Tibullo D., Bucchieri F., Mangiameli A., Parola M., Bugianesi E., Volti G.L., Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis. Digest. Liver Dis., 2012, 44, 334–342.

43. Samuel V.T., Liu Z.X., Qu X., Elder B.D., Bilz S., Befroy D., Romanelli A.J., Shulman G.I., Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J. Biol. Chem., 2004, 279, 32345–32353.

44. Shaw L.M., Stromme J.H., London J.L., Theodorsen L., IFCC methods for the determination of enzymes part 4. IFCC method for gamma-glutamyl transferase [(gamma-glutamyl)-peptide; amino acid gamma-glutamyl transferase, EC 2.3.2.2]. Clin. Chim. Acta, 1983, 135, 315F-338F.

45. Sheth S.G., Gordon F.D., Chopra S., Nonalcoholic steatohepatitis. Ann. Intern. Med., 1997, 126, 2, 137–145.

46. Shulman G.I., Cellular mechanisms of insulin resistance. J. Clin. Invest., 2007, 106, 171–176.

47. Skottova N., Krecman V., Simanek V., Activities of silymarin and its flavonolignans upon low density lipoprotein oxidizability in vitro. Phytother. Res., 1999, 13, 535–537.

48. Skottova N., Vecera R., Urbánek K., Vána P., Walterová D., Cvak L., Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets. Pharmacol. Res., 2003, 47, 17–26.

49. Sobolova L., Skottova N., Vecera R., Urbanek K., Effect of silymarin and its polyphenolic fraction on cholesterol absorbtion in rats. Pharmacol. Res., 2006, 53, 104–112.

50. Soto C., Recoba R., Barrón H., Alvarez C., Favari L., Silymarin increases antioxidant enzymes in alloxan-induced diabetes mellitus in the rat pancreas. Comp Biochem Physiol. C Toxicol. Pharmacol., 2003, 136, 205–212.

51. Soto C., Mena R., Luna J., Cerbón M., Larrieta E., Vital P., Uría E., Sánchez M., Recoba R., Barrón H., Favari L., Lara A., Silymarin induces recovery of pancreatic function after alloxan damage in rats. Life Sci., 2004, 75, 2167–2180.

52. Tanaka S., Hayashi T., Toyoda T., High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle. Metabolism: Clin. Exp., 2007, 56, 1719–1728.

53. Terra X., Pallarés V., Ardèvol A., Bladé C., Fernández-Larrea J., Pujadas G., Salvadó J., Arola L., Blay M., Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. J. Nutr. Biochem., 2011, 22, 380–387.

54. Trappoliere M., Federico A., Tuccillo C., de Sio I., Di Leva A., Niosi M., D’Auria M., Loguercio C., Effects of a new pharmacological complex (silybin + vitamin-E + phospholipids) on some markers of the metabolic syndrome and of liver fibrosis in patients with hepatic steatosis Preliminary study. Minerva Gastroenterol Dieto., 2005, 51, 193–199 (in Italian).

55. Tsai J.H., Liu J.Y., Wu T.T., Ho P.C., Huang C.Y., Shyu J.C., Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. J. Viral Hepat., 2008, 15, 508–514.

56. Vengerovskii A.I., Khazanov V.A., Eskina K.A., Vasilyev K.Y., Effects of silymarin (hepatoprotector) and succinic acid (bioenergy regulator) on metabolic disorders in experimental diabetes mellitus. Bull. Exp. Biol. Med., 2007, 144, 53–56.

57. Wagner H., Seligmann O., Liver therapeutic drugs from Silybum marianum. 1985, in: Advances in Chinese Medicinal Materials Research (eds. H.M. Chang, H.W. Yeung, W.W. Tso, A. Koo). World Scientific Publ., Singapore, pp.132–133.

58. Warnick GR., Wood P.D., National Cholesterol Education Program recommendations for measurement of high-density lipoprotein cholesterol: Executive summary. Clin. Chem., 1995, 41, 1427–1433.

59. Wei Y., Clark S.E., Morris E.M., Thyfault J.P., Uptergrove G.M., Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats. J. Hepatol., 2008, 49, 417–428.

60. Wroblewski F., LaDue J.S., Serum glutamic pyruvic transaminase in cardiac and hepatic disease. Proc. Soc. Exp. Biol. Med., 1956, 91, 569–571.

61. You J.S., Lee Y.L., Kim S.H., Kim S.H., Changa K.J., Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Nutr. Res., 2014, 34, 258–267.

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