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

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 in treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms are still unclear. In t...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430321/
https://www.ncbi.nlm.nih.gov/pubmed/34512330
http://dx.doi.org/10.3389/fphar.2021.693701
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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
author_facet 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
author_sort Wei, Xiaoyi
collection PubMed
description 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 in treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms are still unclear. In this study, we employed a network pharmacology approach consisting of overlapped terms- (genes or pathway terms-) based analysis, protein-protein interaction (PPI) network-based analysis, and PPI clusters identification. Unlike the previous network pharmacology study, we used the 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. The 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 discover potential mechanisms by which SNS ameliorates NAFLD.
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spelling pubmed-84303212021-09-11 Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease 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 Front Pharmacol Pharmacology 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 in treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms are still unclear. In this study, we employed a network pharmacology approach consisting of overlapped terms- (genes or pathway terms-) based analysis, protein-protein interaction (PPI) network-based analysis, and PPI clusters identification. Unlike the previous network pharmacology study, we used the 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. The 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 discover potential mechanisms by which SNS ameliorates NAFLD. Frontiers Media S.A. 2021-08-27 /pmc/articles/PMC8430321/ /pubmed/34512330 http://dx.doi.org/10.3389/fphar.2021.693701 Text en Copyright © 2021 Wei, Hou, Liang, Fang, Dou, Wang, Sai, Xu, Ma, Zhang, Cheng, Wang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
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
Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease
title Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease
title_full Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease
title_fullStr Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease
title_full_unstemmed Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease
title_short Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease
title_sort network pharmacology-based analysis on the potential biological mechanisms of sinisan against non-alcoholic fatty liver disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430321/
https://www.ncbi.nlm.nih.gov/pubmed/34512330
http://dx.doi.org/10.3389/fphar.2021.693701
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