EFFECT OF SUGNIL, A TRADITIONAL ANTIDIABETIC HERBAL FORMULATION ON THE EXPRESSION OF TRANSCRIPTION FACTORS IN STREPTOZOTOCIN DIABETIC RATS.
Objective: A number of large randomized clinical trials demonstrated that lipid lowering successfully reduced cardiovascular events and death in patients with diabetes. Recent studies have reported that multiple transcription factors are involved in regulation of lipid metabolism in diabetic subjects. Numerous plant extracts and formulations have been shown to regulate the expression of transcription factors which in turn normalize lipid abnormalities in diabetic patients. In this series, sugnil, a traditional anti-diabetic polyherbal formulation was assessed for its regulatory effect on the expression of transcription factors in lipid metabolism of streptozotocin induced diabetic rats.
Methods: The mRNA expressions of fatty acid synthesis related genes such as SREPB-1 and SREPB-2 and fatty acid decomposition related gene PPARÎ± were measured by real-time RT-PCR using an appropriate primers and thermal cycler conditions.
Results: Oral administration of sugnil to diabetic rats for 42 consecutive days effectively normalized the expression of these transcription factors to near normal as in control rats. Expression of PPAR-Î± was found to be up-regulated that leads to diminished expression of SREBP-2 in the liver of diabetic rats treated with sugnil. Treatment with sugnil also down regulated the SREBP-1 expression in the kidney of diabetic rats.
Conclusion: The molecular mechanisms of action of sugnil in the regulation the lipid profile in diabetic rats might be normalizing the expression of these transcription factors.
2. Karthikeyan P, Sridhr S, Anuradha CV. Antihyperlipidemic potential of a traditional siddha polyherbal formulation sugnil in streptozotocin-induced diabetic rats. Int J Curr Res 2011;11:331-5.
3. Yechoor VK, Patti ME, Saccone R, Kahn CR. Coordinated pattern of gee expression for substrate and energy metabolism in skeletal muscle of diabetic mice. Proc Natl Acad Sci USA 2002;99:10587â€“92.
4. Sreekumar R, Halvatsiotis P, Schimke JC, Nair KS. Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes 2002;51:1913â€“20.
5. Oâ€™Brien RM, Granner DK. Regulation of gene expression by insulin. Physiol Rev 1996;76:1109â€“61.
6. Kevin Zhe-Yang Xua, Chenchen Zhub, Moon Sun Kima, Johji Yamaharac, Yuhao Li. Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity. J Ethno 2009;123:280â€“7.
7. Teayoun Kim, Jessica Davis, Albert J. Zhang, Xiaoming He, Suresh T. Mathews. Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells. Bioche Biophy Res Com 2009;388:377â€“82.
8. Kwon HJ, Hyun SH, Choung SY. Traditional Chinese Medicine improves dysfunction of peroxisome proliferator-activated receptor alpha and microsomal triglyceride transfer protein on abnormalities in lipid metabolism in ethanol fed rats. Biofactors 2005;23:163â€“76.
9. Torra IP, Chinetti G, Duval C, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice. Curr Opi Lipid 2001;12:242â€“54.
10. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-35.
11. Escher P, Wahli W. Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mut Res 2000;448:121â€“38.
12. Francis GA, Annicotte JS, Auwerx J. PPAR-alpha effects on the heart and other vascular tissues. Am J Phy 2003;285:H1â€“H9.
13. Klaunig JE, Babich MA, Baetcke KP, Cook JC, Corton JC, David RM, et al. PPAR alpha agonist-induced rodent tumors: modes of action and human relevance. Crit Rev Toxi 2003;33:655â€“780.
14. Tom Hsun-Wei Huang, AikWei Teoh, Bei-Lun Lin, Diana Shu-Hsuan Lin, Basil Roufogalis. Review the role of herbal PPAR modulators in the treatment of cardiometabolic syndrome. Pharm Res 2009;60:195â€“206.
15. Brown MS, Goldstein JL. The SREBP Pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 2007;89:331â€“40.
16. Horton JD, Shimomura I. Sterol regulatory element-binding proteins: activators of cholesterol and fatty acid biosynthesis. Curr Opin Lipidol 1999;10:143â€“50.
17. Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS. Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest 1997;99:838â€“42.
18. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002;109:1125â€“31.
19. Rakieten N, Rakieten ML, Nadkarni MV. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep 1963;29:91â€“8.
20. Huang TH, Peng G, Li G Q, Yamahara J, Roufogalis BD, Li Y. Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: activation of PPAR-alpha. Toxicol Appl Pharm 2006;211:225â€“35.
21. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000;405:421â€“4.
22. Konig B, Koch A, Spielmann J, Hilgenfeld C, Gabriele I, Eder K. Activation of PPARa lowers synthesis and concentrationof cholesterol by reduction of nuclear SREBP-2. Biochem Pharm 2007;73:574â€“85.
23. Sun L, Halaihel N, Zhang W, Rogers T, Levi M. Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus. J Bio Chem 2002;277:18919â€“27.
24. Karthikeyan P, Sridhr S, Anuradha CV. Evaluation of antidiabetic efficacy of a siddha polyherbal formulation (sugnil) in streptozotocin induced diabetic rats. Int J Pharm Tech 2011;3:3001-14.