Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2058
Peer-review started: June 19, 2014
First decision: July 21, 2014
Revised: September 3, 2014
Accepted: November 18, 2014
Article in press: November 19, 2014
Published online: February 21, 2015
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 and GP-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-α and NF-κB in the rat liver was analyzed using immunohistochemistry. The expression of proliferator-activated receptor gamma (PPARγ) and cytochrome P450 (CYP450) 1A1 mRNA was determined by quantitative RT-PCR.
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 at 800 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-α and NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner, and the expression of PPARγ and CYP4501A1 mRNA, 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 PPARγ and CYP4501A1 mRNAs.
Core tip: Gypenosides (GPs) are one of the most pharmacologically active components in G. pentaphyllum. Intervention with GPs significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin, triglycerides and total cholesterol in type 2 diabetes mellitus and non-alcoholic fatty liver disease (T2DM-NAFLD) model rats, down-regulated the expression of TNF-α, NF-κB, rabbit anti-proliferator activated receptory (PPARγ) and rabbit anti-cytochrome P4501A1 (CYP1A1) mRNA, decreased the infiltration of liver fats and reversed the histopathological changes in a dose-dependent manner. These findings suggest that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-α and NF-κB proteins, and PPARγ and CYP4501A1 mRNAs.