AUTHOR=Wei Xiaoyi , Hou Weixin , Liang Jiajun , Fang Peng , Dou Bo , Wang Zisong , Sai Jiayang , Xu Tian , Ma Chongyang , Zhang Qiuyun , Cheng Fafeng , Wang Xueqian , Wang Qingguo 

TITLE=Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.693701

DOI=10.3389/fphar.2021.693701

ISSN=1663-9812

ABSTRACT=Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in China. Sinisan (SNS) is a traditional Chinese medicine formula that has been widely used treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms is still unclear. In this study, we employed a network pharmacology approach consisting overlapped terms (genes or pathway terms)-based analysis, protein-protein interaction (PPI) network-based analysis and PPI clusters identification. Unlike previous network pharmacology study, we used a shortest path length-based network proximity algorithm to evaluate the efficacy of SNS against NAFLD. And we also used random walk with restart (RWR) algorithm and Community Cluster (Glay) algorithm to identify important targets and clusters. The screening results showed that the mean shortest path length between genes of SNS and NAFLD was significantly smaller than degree-matched random ones. Six PPI clusters were identified and ten hub targets were obtained, including STAT3, CTNNB1, MAPK1, MAPK3, AGT, NQO1, TOP2A, FDFT1, ALDH4A1 and KCNH2. Experimental study indicated that SNS reduced hyperlipidemia, liver steatosis and inflammation. Most importantly, JAK2/STAT3 signal was inhibited by SNS treatment and was recognized as the most important signal considering the network pharmacology part. This study provides a systems perspective to study the relationship between Chinese medicines and diseases and helps to discovery potential mechanisms by which SNS ameliorates NAFLD.