Gypenosides regulate farnesoid X receptor-mediated bile acid and lipid metabolism in a mouse model of non-alcoholic steatohepatitis

Hongshan Li,Huajie Tian,Yiyang Hu,Yingfei Xi,Xin Xin

doi:10.1186/s12986-020-00454-y

Abstract

BackgroundGypenosides (Gyp) are the main ingredient of the Chinese medicine, Gynostemma pentaphyllum. They are widely used in Asia as a hepatoprotective agent. Here, we elucidated the mechanism of Gyp in non-alcoholic steatohepatitis (NASH) with a focus on farnesoid X receptor (FXR)-mediated bile acid and lipid metabolic pathways.MethodsNASH was induced in mice by high-fat diet (HFD) feeding, while mice in the control group were given a normal diet. At the end of week 10, HFD-fed mice were randomly divided into HFD, HFD plus Gyp, and HFD plus obeticholic acid (OCA, FXR agonist) groups and were given the corresponding treatments for 4 weeks. Next, we analyzed the histopathological changes as well as the liver triglyceride (TG) level and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG), fasting insulin (FINS), TG, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels as well as the bile acid profile. We carried out RT-PCR and western blotting to detect HFD-induced alterations in gene/protein expression related to bile acid and lipid metabolism.ResultsThe HFD group had histopathological signs of hepatic steatosis and vacuolar degeneration. The liver TG and serum ALT, AST, FBG, FINS, TC, and LDL-C levels as well as the total bile acid level were significantly higher in the HFD group than in the control group (P < 0.01). In addition, we observed significant changes in the expression of proteins involved in bile acid or lipid metabolism (P < 0.05). Upon treatment with Gyp or OCA, signs of hepatic steatosis and alterations in different biochemical parameters were significantly improved (P < 0.05). Further, HFD-induced alterations in the expression genes involved in bile acid and lipid metabolism, such as CYP7A1, BSEP, SREBP1, and FASN, were significantly alleviated.ConclusionsGyp can improve liver lipid and bile acid metabolism in a mouse model of NASH, and these effects may be related to activation of the FXR signaling pathway.

Highlights

Gypenosides (Gyp) are the main ingredient of the Chinese medicine, Gynostemma pentaphyllum
Dietary intake and activity level of mice Our results demonstrated that the dietary intake of mice in the high-fat diet (HFD) group was higher than that of mice in control group (P < 0.01)
Impact of gyp treatment on the liver index and mice weight Compared to the control group, mice in the HFD group had a significantly higher body weight starting from weeks 10–14 (Fig. 2a, P < 0.01)

Summary

Introduction

Gypenosides (Gyp) are the main ingredient of the Chinese medicine, Gynostemma pentaphyllum. They are widely used in Asia as a hepatoprotective agent. Non-alcoholic fatty liver disease (NAFLD) is a complication of obesity and metabolic syndromes [1]. The clinical presentation of NAFLD ranges from simple steatosis and non-alcoholic fatty liver to hepatic fibrosis [2]. Hepatic fibrosis and non-alcoholic steatohepatitis (NASH) are among the main reasons for the development of liver cirrhosis and hepatocellular carcinoma [3, 4]. Dietary adjustments and lifestyle changes are the standard treatment strategies for NASH, while efficient therapeutic agents are not yet available in clinical practice [6]

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