Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

• Published in: World journal of gastroenterology : WJG Vol. 21; no. 7; pp. 2058 - 2066
• Main Authors: He, Qin, Li, Jin-Ke, Li, Fang, Li, Ru-Gui, Zhan, Guo-Qing, Li, Gang, Du, Wei-Xing, Tan, Hua-Bing
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 21.02.2015
• Subjects: Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Basic Study; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Gynostemma; Gypenosides;Type; Insulin - blood; Lipids - blood; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; mellitus;Non-alcoholic; NF-kappa B - metabolism; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - pathology; Plant Extracts - pharmacology; PPAR gamma - genetics; PPAR gamma - metabolism; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Time Factors; Tumor Necrosis Factor-alpha - metabolism; Non-alcoholic fatty liver; Type 2 diabetes mellitus; Gypenosides; Cytochrome P4501A1; PPARγ
• DOI: 10.3748/wjg.v21.i7.2058
• ISSN: 1007-9327

AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in rats.METHODS:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment groups.The study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry.The expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative RTPCR.RESULTS:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(P<0.05,P<0.01),especially at the dose of 800 mg/kg per day.To a similar extent,GP at800 mg/kg per day reduced the levels of BG(4.19±0.47,P<0.01),TG(80.08±10.05,P<0.01),TC(134.38±16.39,P<0.01)and serum insulin(42.01±5.04,P<0.01).The expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner,and the expression of PPARγand CYP4501A1 m RNA,as measured using quantitative real-time PCR,were significantly down-regulated by GPs.Moreover,GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner.CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.