Mechanism Study of Xiaoyao San against Nonalcoholic Steatohepatitis-Related Liver Fibrosis Based on a Combined Strategy of Transcriptome Analysis and Network Pharmacology

Author:

Yan Di123,Zhang Xiaoling3,Ma Chengmei3,Huang Wenting2,Hao Mimi3,Xie Lan23ORCID

Affiliation:

1. School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

2. Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing 100084, China

3. National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine (TCM) formula that has been widely used in treating liver diseases. In this study, we elucidated the effects and mechanism of XYS in treating NASH-related liver fibrosis by combining high-throughput sequencing-based high-throughput screening with network pharmacology analysis. Our work revealed that XYS may play a role in preventing NASH-related liver fibrosis by regulating biological functions related to the extracellular matrix (ECM), inflammation, and metabolism. Additionally, Bupleuri Radix, Poria, Zingiberis Rhizoma Recens, and Paeoniae Radix Alba are the key herbs of XYS that could partially represent the functions of XYS. These regulatory effects are mediated by targeting signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NFκB), and peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Narcissin, casuarictin, and γ-sitosterol were identified as representative active compounds in XYS targeting STAT3, NFκB, and PPARγ, respectively. Taken together, our findings provide a novel strategy for investigating the pharmacological effects and biological mechanisms of a TCM formula.

Funder

Strategic Consulting Projects of Chinese Academy of Engineering

Publisher

MDPI AG

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