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. 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 of the cathepsins were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using immunohistochemistry. The expression of proliferativated receptor gamma (PPARγ) and cytochrome P450 (CYP450) 1A1 m RNA was determined by quantitative RTPCR.RESULTS : GP treatments at oral doses of 200,400, and 800 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 red The level of BG was significantly higher than that of the control group (4.19 ± 0.47, P <0.01), TG (80.08 ± 10.05, P <0.01) and TC (134.38 ± 16.39, P <0.01) expression of TNF-αand NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner, and the expression of PPARγ and 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 dose dependent manner. CONCLUSION: This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-α and NF-κB proteins, and PPARγand CYP4501A1 m RNAs.