基于网络药理学和分子对接法探讨消肿汤治疗痔病的作用机制

Mechanism of Xiaozhong Tang in treatment of hemorrhoids based on network pharmacology and molecular docking

目的基于网络药理学及分子对接法探讨自拟中医方剂消肿汤治疗混合痔的作用机制。方法应用中药系统药理学数据库与分析平台(TCMSP)获得消肿汤各药物的有效成分及作用靶点,并通过UniProt数据库校正蛋白名称。通过GeneCards、OMIM、TTD、DrugBank、DisGeNET数据库获取痔病疾病靶点,取二者靶点交集。通过STRING数据库、Cytoscape软件建立蛋白质相互作用(PPI)网络,得出核心靶点。应用Metascape数据库对共有靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路分析。最后将药物的核心成分与核心靶点上传至CB-Dock2平台进行分子对接验证。结果全方筛选共得到136个药物有效成分、233个药物靶点,获取疾病靶点638个,其中共有靶点45个;PPI分析后经拓扑特征分析得到基质金属蛋白酶-9(matrix metalloproteinase-9,MMP9)、细胞肿瘤抗原p53(tumor protein p53,TP53)等9个核心靶点。GO及KEGG富集分析显示,消肿汤治疗混合痔可能与脂质和动脉粥样硬化、IL-17信号通路、HIF-1信号通路等相关。分子对接结果显示,α-菠菜甾醇、黄芩素、汉黄芩素等核心成分与痔病的MMP9、TP53、1L1B等靶点对接结合活性良好。结论消肿汤通过多成分、多靶点、多通路治疗痔病,为消肿汤治疗痔病提供了理论支持。

Objective To investigate the mechanism of the self-formulated traditional Chinese medicine formula Xiaozhong Tang in the treatment of hemorrhoids based on the network pharmacology and molecular docking.Methods The active ingredients and target proteins of Xiaozhong Tang were obtained from the Traditional Chinese Medicine System Pharmacology and Pharmacokinetics Database and Analysis Platform(TCMSP),and the protein names were corrected using the UniProt database.The disease targets of hemorrhoids were obtained from the GeneCards,OMIM,TTD,DrugBank,and DisGeNET databases,and the intersections of the two target sets were obtained.The protein-protein interaction(PPI)network was established using the STRING database and Cytoscape software,and the core targets were obtained.The shared targets were subjected to the Gene Ontology(GO)function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis using the Metascape database.Finally,the core components and core targets were uploaded to the CB-Dock2 platform for molecular docking verification.Results A total of 136 active ingredients and 233 target proteins were identified from the whole formula,and 638 disease targets were obtained.There were 45 shared targets.After PPI analysis and topological feature analysis,matrix metalloproteinase-9(MMP9),tumor protein p53(TP53),etc.were identified as the 9 core targets.The GO and KEGG enrichment analysis showed that Xiaozhong Tang may be related to lipid and atherosclerosis,IL-17 signaling pathway,and HIF-1 signaling pathway in the treatment of hemorrhoids.The molecular docking results showed that the core components,such asα-spinach sterol,baicalin,hanbaicalin,etc.,had good binding activity with the MMP9,TP53,and IL1B targets of hemorrhoids.Conclusion Xiaozhong Tang treats hemorrhoids through multiple components,multiple targets,and multiple pathways,and provides theoretical support for its clinical treatment of hemorrhoids.