Exploring therapeutic mechanisms of San-Huang-Tang in nonalcoholic fatty liver disease through network pharmacology and experimental validation
Exploring therapeutic mechanisms of San-Huang-Tang in nonalcoholic fatty liver disease through network pharmacology and experimental validation
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通过网络药理学和实验验证探讨三黄汤治疗非酒精性脂肪肝的治疗机制
DOI：
10.1016/j.jep.2022.115477
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yuanyuan Chen
中科院分区：
文献类型：
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作者：
Huilian Shi;Fei Qiao;Kaiyue Huang;Weiting Lu;Xinzhuang Zhang;Zhipeng Ke;Yanchi Wu;Liang Cao;Yuanyuan Chen
三黄汤是一种传统的中药方剂，临床上用于治疗肥胖症和2型糖尿病。近年来研究表明，SHT对非酒精性脂肪性肝病（NAFLD）有较好的治疗作用，本研究旨在探讨SHT抗NAFLD的作用机制。通过网络药理学平台获得SHT的数据，并进行体内外实验验证，通过网络药理学分析预测SHT的候选靶点，通过蛋白质-蛋白质相互作用（PPI）网络筛选关键靶点。应用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析SHT对NAFLD相关信号通路的影响，并通过体内外分子生物学实验对分析结果进行验证，通过网络药理学分析筛选分子，通过IPITTs和IPGTTs检测其对NAFLD小鼠胰岛素抵抗的改善作用。通过一系列的分子生物学实验，发现SHT可以增加胰岛素受体（INSR）和胰岛素受体底物（IRS 1）的转录，增强苏氨酸蛋白激酶（AKT）和叉头盒O 1（FoxO 1）的磷酸化，并通过生物信息学筛选和体内外实验验证，SHT可能通过激活INSR/IRS 1/AKT/FoxO 1信号通路影响胰岛素抵抗，从而导致NAFLD的发生。本研究结果不仅为SHT的治疗作用提供了实验依据，也为SHT治疗NAFLD提供了新的靶点。
San-Huang-Tang (SHT), a traditional Chinese medicine (TCM) formula, has been clinically used to treat obesity and type 2 diabetes mellitus. Recently it has proved that SHT have a good effect on non-alcoholic fatty liver disease (NAFLD).Our study was designed to investigate the therapeutic mechanisms of the SHT against NAFLD. The data of SHT were obtained through network pharmacology platform and validated experimentally in vivo and in vitro.The candidate targets of SHT were predicted by network pharmacological analysis and crucial targets were chosen by the protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto encyclopedia of genes and Genomes (KEGG) were applied to analyze the NAFLD-related signaling pathways affected by SHT, and then the analysis results were verified with molecular biological experiments in vivo and in vitro.Molecules were screened with network pharmacological analysis, and then the improvement of insulin resistance of NAFLD mice was measured by IPITTs and IPGTTs. Through series of molecular experiments, it is revealed that SHT could increase the transcription of insulin receptor (INSR) and insulin receptor substrate (IRS1), and enhance the phosphorylation of both threonine protein kinase (AKT) and forkhead box O1 (FoxO1).Screened by bioinformatics and verified by experiments in vivo and in vitro, SHT could contribute to NAFLD by affecting insulin resistance via activating INSR/IRS1/AKT/FoxO1 pathway. Our research findings provide not only an experimental basis for the therapeutic effect of SHT but also a new target against NAFLD.