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目的:以中医“异病同治”理论为依据，采用网络药理学-分子对接方法探讨四逆散“异病同治”溃疡性结肠炎和肠易激综合征的作用靶点及可能作用机制。方法:通过TCMSP等中药化合物数据库结合文献挖掘获取四逆散的化学成分和作用靶点；结合GeneCards、OMIM、DRUGBANK、TTD等数据库获取四逆散治疗溃疡性结肠炎和肠易激综合征的作用靶点。采用Cytoscape软件绘制四逆散“中药-成分-靶点”网络及“中药-共有靶点-疾病”网络。借助STRING数据库及Cytoscape软件构建PPI网络，分析获得核心作用靶点。采用Metascape平台工具对四逆散治疗溃疡性结肠炎和肠易激综合征的共有靶点进行GO分析、KEGG通路分析等。使用AutodockTools软件对四逆散主要活性成分与作用靶点进行分子对接。结果:筛选得到四逆散化学成分144个，对应靶点257个，溃疡性结肠炎331个，肠易激综合征866个，以及44个药物成分和疾病共同靶点。PPI网络中关键蛋白排名靠前的几个靶点为TP53、AKT1、IL-6、TNF;获得GO、KEGG富集分析结果排名靠前的有20种生物过程、15种分子功能、8种细胞组分及22条信号通路。KEGG分析其调节的通路主要与PI3K-AKT信号通路、IL-17信号通路、TNF信号通路、JAK-STAT信号通路等密切相关。分子对接结果显示关键成分与对应靶点具有较好的结合活性。结论:四逆散治疗溃疡性结肠炎和肠易激综合征可能涉及以TP53、AKT1、IL-6、TNF等核心靶点为代表，其实现异病同治的作用可能与调控PI3K-AKT、TNF、JAK-STAT等信号通路有关。
Abstract：Objective: To discuss the targets and possible mechanisms of Sini Powder(四逆散) in treating ulcerative colitis and irritable bowel syndrome through homotherapy for heteropathy(treating different diseases with the same method) based on network pharmacology and molecular docking. Methods: The chemical components and targets of Sini Powder were retrieved from databases on the chemical component of Chinese medicine such as TCMSP and literature and targets of Sini Powder for treating ulcerative colitis and irritable bowel syndrome from GeneCards, OMIM,DRUGBANK,and TTD. Cytoscape was employed to plot the "Chinese medicinal-component-target" network of Sini Powder and "Chinese medicinal-common target-disease" network, and STRING and Cytoscape to establish the protein-protein interaction(PPI) network. Thereby, the hub genes were identified. Metascape was adopted for the analysis of GO terms and KEGG pathways related to the targets of Sini Powder for treating both ulcerative colitis and irritable bowel syndrome, and AutodockTools for the molecular docking of main active components of Sini powder and common targets. Results: A total of 144 chemical components and 257 targets of Sini Powder, 331 targets of ulcerative colitis, and 866 targets of irritable bowel syndrome were retrieved, and 44 common targets of the prescription components and diseases were identified. According to the PPI network, the major targets were TP53,AKT1,IL-6,and TNF,and they were related to 20 biological processes, 15 molecular functions, 8 cellular components, and 22 KEGG pathways, of which the main pathways were PI3 K-Akt, IL-17,TNF,and JAK-STAT signal pathways. Molecular docking validated the strong binding interactions between the key components and corresponding targets. Conclusion: The therapeutic effect of Sini Powder on ulcerative colitis and irritable bowel syndrome may involve core targets such as TP53,AKT1,IL-6,and TNF,and the simultaneous treatment of different diseases may be related to the regulation of PI3 K-Akt, TNF,JAK-STAT,and other signal pathways.
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基本信息:
DOI：10.13412/j.cnki.zyyl.20210806.010
中图分类号:R285.5
引用信息:
[1]卢鑫,张馨月,林逸婷,等.基于网络药理学-分子对接探讨四逆散“异病同治”溃疡性结肠炎和肠易激综合征的作用机制[J].中药药理与临床,2022,38(04):167-174.DOI:10.13412/j.cnki.zyyl.20210806.010.
基金信息:
国家自然科学基金项目(编号：81260536); 广西自然科学基金项目(编号：2018GXNSFAA281042); 广西中医药大学2020年校级硕士研究生科研创新项目(编号：xjyb112)
2021-08-09
2021-08-09
2021-08-09