Lingguizhugan Decoction Protects against High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease by Alleviating Oxidative Stress and Activating Cholesterol Secretion.

Lili Yang,Peiyong Zheng,Shijun Hao,Haiyan Song,Colleen A Nugent,Weili Lin,Tao Liu

doi:10.1155/2017/2790864

Abstract

Background Nonalcoholic fatty liver disease (NAFLD) has become a leading cause of liver transplantation. Lingguizhugan decoction (LGZG), a classical Chinese herbal formula, has beneficial effects on NAFLD animal models. Our study examined the impact of LGZG on hepatic global transcriptome of high-fat-diet-induced NAFLD rats. Methods Three groups of Wistar rats were included: normal, NAFLD model, and LGZG-treated NAFLD groups. Four weeks for the treatment, liver tissues were harvested for RNA sequencing. Differentially expressed genes (DEGs) and enriched pathways were detected on hepatic global transcriptome profile. Real-time PCR validated the regulatory patterns of LGZG on NAFLD rats. Results DEGs between the NAFLD model and normal groups indicated the elevated peroxisome proliferator-activated receptor (PPAR) and hedgehog signaling pathways in NAFLD rats. In bile secretion pathway, genes involved in cholesterol secretion were activated by LGZG treatment. Increased expression of antioxidant OSIGN1 and decreased expression of genes (AHR, IRF2BP2, and RASGEF1B) that induce oxidative stress and inflammation were observed in NAFLD rats treated with LGZG. The regulatory patterns of LGZG treatment on these oxidative stress-related genes were confirmed by real-time PCR. Conclusion Our study revealed a “two-hits-targeting” mechanism of LGZG in the treatment for NAFLD: alleviating oxidative stress and activating cholesterol secretion.

Highlights

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathological conditions, including simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis
According to the “two-hits” hypothesis of NAFLD pathogenesis, the first hit is represented by lipid accumulation in the hepatocytes, after which oxidative stress leads to severe NASH [2]
A total of 24 male Wistar rats with weights of 130 g ± 10 g in specific pathogen free (SPF) grade were purchased from Shanghai Si-Lai-Ke Experimental Animal Ltd. (Shanghai, China)

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathological conditions, including simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Many potential targets for the treatment of NAFLD are identified, including lipid metabolism, oxidative stress, inflammation, fibrosis, and altered gut microbiota [9]. Three groups of Wistar rats were included: normal, NAFLD model, and LGZG-treated NAFLD groups. Real-time PCR validated the regulatory patterns of LGZG on NAFLD rats. Genes involved in cholesterol secretion were activated by LGZG treatment. Increased expression of antioxidant OSIGN1 and decreased expression of genes (AHR, IRF2BP2, and RASGEF1B) that induce oxidative stress and inflammation were observed in NAFLD rats treated with LGZG. The regulatory patterns of LGZG treatment on these oxidative stress-related genes were confirmed by real-time PCR. Our study revealed a “two-hits-targeting” mechanism of LGZG in the treatment for NAFLD: alleviating oxidative stress and activating cholesterol secretion

Methods

Results

Conclusion