Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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Protective effect of silymarin in streptozotocin-induced diabetic dyslipidaemia in rats

  • Sharma, Manju (Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University)) ;
  • Pillai, K.K. (Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University)) ;
  • Anwer, Tarique (Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University)) ;
  • Najmi, Abul Kalam (Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University)) ;
  • Haque, Syed Ehtaishamul (Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University)) ;
  • Sultana, Yasmin (Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University))
  • Received : 2009.03.18
  • Accepted : 2010.07.23
  • Published : 2010.09.30
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Abstract

The present study investigated the effect of silymarin, a flavonoid, on streptozotocin (STZ) - induced diabetic dyslipidaemia in rats. Experimental diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Silymarin (25 mg/kg and 50 mg/kg) was orally administered to diabetic rats for a period of 15 days. Blood glucose levels, serum lipid profile and liver glycogen levels were estimated following the established procedures. Biochemical observations were supplemented with histological examination of liver sections. Oral administration of silymarin to diabetic rats significantly (P < 0.001) decreased the blood glucose levels ($259.99{\pm}23.64$ vs. $99.90{\pm}2.62$ [25 mg] & $89.17{\pm}3.32$ [50 mg]). The most interesting finding was the significant (p < 0.001) increase in HDL-cholesterol levels ($26.99{\pm}0.61$ vs. $40.55{\pm}0.52$ [25 mg] & $41.12{\pm}0.37$ [50 mg]) whereas, there was a significant decrease in serum total cholesterol (TCh), triglycerides (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol levels observed in silymarin treated diabetic rats. STZ treatment caused significant degeneration of liver parenchyma, which was normalized to near normal morphology by administration of silymarin. The findings indicate that silymarin effectively improved the overall lipid profile and restored the glycogen stores in the liver of STZ-induced diabetic rats, in a dose dependent manner. The results indicate existence of abnormalities in lipid metabolism in STZ-induced diabetic rats and suggest a protective effect of silymarin in this animal model.

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References

  1. Adeneye AA, Adeleke TI, Adeneye AK. (2008) Hypoglycemic and hypolipidemic effects of the aqueous fresh leaves extract of Clerodendrum capitatum in Wistar rats. J. Ethnopharmacol. 116, 7-10. https://doi.org/10.1016/j.jep.2007.10.029
  2. Alzaharani T, Marrat S, Haider A. (2003) Management of dyslipidaemia in primary care. Can. J. Cardiol. 3, 356-360.
  3. Anila L, Vijayalakshmi NR. (2002) Flavonoids from Emblica officinalis and Mangifera indica - effectiveness for dyslipidaemia. J. Ethnopharmacol. 79, 81-87. https://doi.org/10.1016/S0378-8741(01)00361-0
  4. Barnett A. (2001) Type 2 diabetes and cardiovascular disease. Nursing Times 97, 33-35.
  5. Barrett-Connor E, Grundy SM, Holdbrook MJ. (1982) Plasma lipids and diabetes mellitus in an adult community. Am. J. Epidemiol. 115, 657-663. https://doi.org/10.1093/oxfordjournals.aje.a113348
  6. Best J D and O’Neal DN. Diabetic Dyslipidaemia: Current treatment recommendations, Drugs 59, 1101-1110. https://doi.org/10.2165/00003495-200059050-00006
  7. Betteridge J. (1997) Lipid disorders in diabetes mellitus. In: Pickup, JC, Williams, G. (Eds.), Textbook of Diabetes, 31, second ed. Blackwell Science, London, pp. 1-55.
  8. Bindoli A, Cavallini L, Siliprandi N. (1977) Inhibitory action of silymarin of lipid peroxide formation in rat liver mitochondria and microsomes. Biochem. Pharmacol. 26, 2405-2409. https://doi.org/10.1016/0006-2952(77)90449-X
  9. Braham D, Trinder P. (1972) An improved colour reaction for the determination of blood glucose by oxidase system. Analyst 97, 142-144. https://doi.org/10.1039/an9729700142
  10. Bucolo G, David M. (1973) Quantitative determination of serum triglycerides by use of enzymes. Clin. Chem. 19, 476-482.
  11. Chait A, Brazg RL, Tribble DL, Witztum JL, Krauss RM. (1993) Susceptibility of small, dense, LDL to oxidative modification in subjects with the atherogenic lipoprotein phenotype pattern B. Am. J. Med. 94, 350-356. https://doi.org/10.1016/0002-9343(93)90144-E
  12. Dixit N, Baboota S, Kohli K, Ahmad S, Ali J. (2007) Silymarin: A review of pharmacological aspects and bioavailability enhancement approaches. Ind. J. Pharmacol. 39, 172-179. https://doi.org/10.4103/0253-7613.36534
  13. Friedwald WT, Levy RL, Fredrickson DS. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin. Chem. 18, 499-502.
  14. Greimel A, Koch H. (1977) Silymarin-an inhibitor of horseradish peroxidase. Experientia 33, 1417-1418. https://doi.org/10.1007/BF01918777
  15. Haffner S. (1999) Diabetes, hyperlipidemia, and coronary artery disease. Am. J. Cardiol. 83, 17F-21F.
  16. Hegele RA. (1999) Paraoxonase-genes and disease. Annual Med. 31, 217-214. https://doi.org/10.3109/07853899909115981
  17. Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M. (2006) The efficacy of silybum marianum (L). Gaertn. (silymarin) in the treatment of type 2 diabetes: a randomized, doubleblind, placebo-controlled, clinical trial. Phytotherapy Res. 20, 1036-1039. https://doi.org/10.1002/ptr.1988
  18. Matsuda T, Ferrei K, Todorov I , Kuroda Y, Smith CV, Kandeel F, Muller Y. (2005) Silymarin protects pancreatic beta cells against cytokine–mediated toxicity: implication of C-Jun NH2–terminal kinase and janus kinase/signal transducer and activator of transcription pathways. Endrocrinology 146, 175-179. https://doi.org/10.1210/en.2004-0850
  19. Montgomery R. (1957) Determination of Glycogen. Arch. Biochem. Biophys. 67, 378-86. https://doi.org/10.1016/0003-9861(57)90292-8
  20. Mourelle M, Muriel P, Favari L, Franco T. (1989) Prevention of CCI4 induced liver cirrhosis by silymarin. Fundament. Clin. Pharmacol. 3, 183-191. https://doi.org/10.1111/j.1472-8206.1989.tb00449.x
  21. Muriel P, Garciapina T, Perez V, Mourelle M. (1992) Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J. Appl. Toxicol. 12, 439-442. https://doi.org/10.1002/jat.2550120613
  22. Muriel P, Mourelle M. (1990) Prevention by silymarin of membrane alteration in acute CCl4 liver damages. J. Applied. Toxicol. 10, 275-279. https://doi.org/10.1002/jat.2550100408
  23. Navab M, Berliner JA, Watson AD, Hama SY, Territo MC, Lusis AJ, Shih DM, Van Lenten BJ, Frank JS, Demer LL, Edwards PA, Fogelman AM. (1996) The yin and the yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscl. Thromb. Vascul. Biol. 16, 831-842. https://doi.org/10.1161/01.ATV.16.7.831
  24. Paya M, Fernandiz ML, Sanz MJ, Alcaraz MJ. (1993) Effects of phenolic compounds on bromobenzene mediated hepatotoxicity in mice. Xenobiotica 23, 327-333. https://doi.org/10.3109/00498259309059386
  25. Pyolara K, Pedersen TK, Kjeshus J, Faergeman O Oisson AG, Thorgeirsson G. (1997) Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabetes Care 20, 614-620. https://doi.org/10.2337/diacare.20.4.614
  26. Sathishekar D and Subramanian S. (2005) Beneficial effects of momordica charantia seeds in the treatment of STZ-induced diabetes in experimental rats. Biol. Pharm. Bull. 28, 978-982. https://doi.org/10.1248/bpb.28.978
  27. Shukla R, Gupta S, Gambhir JK ,Prabhu KM , Murthy PS .(2004) Antioxidant effect of aqueos extract of the bark of ficus bengalensis in hypercholesterolemic rabbits, J. Ethnopharmacol. 92, 47-50. https://doi.org/10.1016/j.jep.2004.01.020
  28. Shukla, Sharma SB, Puri D, Prabhu KM, Murthy PS. (2000) Medicinal plants for treatment of diabetes mellitus. Ind J. Clin. Biochem. 15, 169-171. https://doi.org/10.1007/BF02867556
  29. Schonfeld JV, Weisbrod B, Muller MK. (1997) Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cell. Mol. Life Sci. 53, 917-920. https://doi.org/10.1007/s000180050111
  30. Schwartz SL. (2006) Diabetes and dyslipidemia. Diabet. Obes. Metab. 8, 355-364. https://doi.org/10.1111/j.1463-1326.2005.00516.x
  31. Sharma M, Anwer T, Pillai KK, Haque SE, Najmi AK, Sultana Y. (2008) Silymarin, a flavonoid antioxidant, protects streptozotocin-induced lipid peroxidation and β-cell damage in rat pancreas. Orient. Pharm. Exp. Med. 8, 146-153. https://doi.org/10.3742/OPEM.2008.8.2.146
  32. Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, Cheroutre H, Faull KF, Berliner JA, Witztum JL, Lusis AJ. (2000) Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J. Biol. Chem. 276, 17527-17535.
  33. Stamler J, Vaccaro O, Neaton JD, Wentworth D. (1993) Diabetes, other risk factors, and 12-years cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes. Care. 16, 434-444. https://doi.org/10.2337/diacare.16.2.434
  34. Steinberg D, Parthasaramy S, Cary TE, Khoo JC, Witztum JJ. (1989) Beyond Cholesterol. Modification of low-density lipoprotein that increase its atherogenicity. New Eng. J. Med. 30, 915-914.
  35. Tan BK, Tan CH, Pushparaj PN. (2005) Anti-diabetic activity of the semipurified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin induced diabetic rats. Life Sci. 76, 2827-2839. https://doi.org/10.1016/j.lfs.2004.10.051
  36. Valsa AK, Ushakumary B, Vijayalakshmi NR. (1995) Effect of catechin on lipid metabolism. J. Clin. Biochem. Nutr. 19, 175-182. https://doi.org/10.3164/jcbn.19.175
  37. Warnick GR, Nguyen T, Albers AA. (1985) Comparison of improved precipitation methods for quantification of high-density lipoprotein cholesterol. Clin. Chem. 31, 217-222.
  38. Witztum L, Steinberg D. (1991) Role of oxidized lowdensity lipoprotein in atherogenesis. J. Clin. Invest. 88, 1785-1792. https://doi.org/10.1172/JCI115499
  39. Wybenga DR, Pileggi VJ, Dirstine PH, Di Glorgio J. (1970) Direct manual determination of serum total cholesterol with a single stable reagent. Clin. Chem. 16, 980-984.