基于网络药理学及分子对接研究大黄治疗肠梗阻的作用机制

Mechanism of action of Rheum officinale in treatment of intestinal obstruction based on network pharmacology and molecular docking

目的:采用网络药理学及分子对接方法探讨大黄治疗肠梗阻的作用机制,为临床应用大黄治疗肠梗阻提供依据。方法:通过TCMSP数据库获得大黄的活性成分与作用靶基因,通过GeneCards、OMIM数据库获取肠梗阻的潜在作用靶点,取二者交集获得交集基因,运用Cytoscape软件构建大黄-活性成分-肠梗阻-靶基因网络图,在STRING平台制作蛋白互作网络,通过Metascape平台对交集靶点进行富集分析,获得靶点功能及通路。最后运用Vina等软件对大黄的关键活性成分与关键靶点进行分子对接验证。结果:筛选得到大黄7个活性成分(芦荟大黄素、β-谷甾醇、泽兰黄醇等),涉及47个作用靶点(JUN、CASP3、MYC、PTGS2、ESR1、IL-1B、CDKN1A、CCNB1、CASP8、CASP9等),主要涉及炎性信号通路、癌症通路。结论:大黄治疗肠梗阻具有多成分、多靶点、多途径的特点。

Objective: To investigate the mechanism of action of Rheum officinale in the treatment of intestinal obstruction based on network pharmacology and molecular docking, and to provide a basis for the clinical application of Rheum officinale in the treatment of intestinal obstruction.Methods: TCMSP database was used to obtain the active components and action targets of Rheum officinale, and GeneCards and OMIM databases were used to obtain the potential targets of intestinal obstruction.Intersecting targets of these two groups of targets were obtained, and Cytoscape software was used to establish a Rheum officinale-active component-intestinal obstruction-target gene network.The STRING platform was used to construct a protein-protein interaction network, and the Metascape platform was used to perform enrichment analysis of the intersecting targets to obtain the functions and pathways of targets.Vina and other software were used to perform molecular docking verification of the key active components and targets of Rheum officinale.Results: A total of 7 active components were screened out, including aloe-emodin, beta-sitosterol, and eupatin, which involved 47 action targets(such as JUN,CASP3,MYC,PTGS2,ESR1,IL-1 B,CDKN1 A,CCNB1,CASP8,and CASP9),mainly involving the inflammatory signaling pathway and the cancer pathway.Conclusion: Rheum officinale has the features of multiple components, targets, and pathways in the treatment of intestinal obstruction.