Salidroside improves high-fat diet-induced non-alcoholic steatohepatitis by regulating the gut microbiota-bile acid-farnesoid X receptor axis

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

doi:10.1016/j.biopha.2020.109915

Salidroside improves high-fat diet-induced non-alcoholic steatohepatitis by regulating the gut microbiota-bile acid-farnesoid X receptor axis

Biomed Pharmacother. 2020 Apr:124:109915. doi: 10.1016/j.biopha.2020.109915. Epub 2020 Jan 25.

Authors

Hongshan Li¹, Yingfei Xi², Xin Xin³, Huajie Tian³, Yiyang Hu⁴

Affiliations

¹ Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Liver Disease Department, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, 315010, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, Zhejiang, 315010, China. Electronic address: lihongshan_1982@126.com.
² Medical School of Ningbo University, Ningbo, Zhejiang, 315211, China.
³ Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁴ Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: yyhuliver@163.com.

PMID: 31986416
DOI: 10.1016/j.biopha.2020.109915

Abstract

Background: Our previous studies found that salidroside can effectively treat non-alcoholic steatohepatitis (NASH). Here, we discuss the mechanism of salidroside in the treatment of NASH with a focus on the gut microbiota-bile acid-farnesoid X receptor axis.

Methods: A NASH mouse model was created by providing mice with a high-fat diet (HFD) for 14 weeks. Mice were randomly divided into the HFD group, HFD + salidroside treatment group, and HFD + obeticholic acid treatment group (n = 8 in each group) and were intragastrically administered corresponding drugs for 4 weeks. Hematoxylin-eosin staining was performed to evaluate the histopathological changes associated with the various treatments. In addition, liver triglyceride (TG) content, serum alanine aminotransferase (ALT) activity, serum inflammatory factors, gut microbiota diversity, and the bile acid profile were evaluated. Western blotting and RT-PCR were performed to detect the expressions of FXR and fibroblast growth factor 15 (FGF15).

Results: The HFD group displayed obvious signs of hepatic steatosis. The liver TG, serum ALT, and IL-1a, IL-12, MCP-1, KC, MIP-1a, and MIP-1β were significantly higher in the HFD group than the control group (P < 0.01). Intestinal bacteria and bile acid profiles changed significantly in the HFD group (P < 0.05). Further, the expressions of FXR and FGF15 decreased significantly in the HFD group (P < 0.05). After treatment with salidroside, liver steatosis, TG content, and serum inflammatory factors significantly improved and HFD-induced intestinal bacteria, bile acid disorder, and FXR deficiency were significantly alleviated (P < 0.05).

Conclusion: Salidroside can improve NASH via the gut microbiota-bile acid-FXR axis.

Keywords: Bile acid; Farnesoid X receptor; Gut microbiota; Non-alcoholic steatohepatitis; Salidroside.

MeSH terms

Animals
Bile Acids and Salts / metabolism
Diet, High-Fat / adverse effects
Disease Models, Animal
Gastrointestinal Microbiome*
Glucosides / pharmacology*
Male
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease / drug therapy*
Non-alcoholic Fatty Liver Disease / microbiology
Non-alcoholic Fatty Liver Disease / physiopathology
Phenols / pharmacology*
Receptors, Cytoplasmic and Nuclear / metabolism
Triglycerides / metabolism

Substances

Bile Acids and Salts
Glucosides
Phenols
Receptors, Cytoplasmic and Nuclear
Triglycerides
farnesoid X-activated receptor
rhodioloside