基于网络药理学和分子对接探讨四逆散干预肠易激综合征作用机制

Mechanism of Sini Powder on treating irritable bowel syndrome based on network pharmacology and molecular docking

目的应用网络药理学及分子对接探讨四逆散从缓解消化道症状及精神神经症状方面综合干预肠易激综合征的分子作用机制。方法检索TCMSP数据库获取四逆散的主要活性成分及其靶点,GeneCards数据库及疗效药靶数据库(TTD)获取肠易激综合征的靶基因,利用STRING数据库及Cytoscape软件构建蛋白相互作用网络并筛选出核心基因,基于CB-Dock在线对接工具进行核心靶点-药物成分的分子对接验证,运用DAVID和Metascape数据库分别进行GO和KEGG通路分析。结果共获得四逆散活性成分112个及作用靶点204个,肠易激综合征相关靶基因2805个,中药-疾病交集靶点152个,主要涉及IL-17信号通路、NF-κB信号通路、VEGF信号通路、多巴胺能突触通路、血清素突触通路和钙信号通路。结论四逆散可通过多成分、多靶点、多途径调节神经内分泌通路、调节免疫平衡、改善肠道轻度炎症和修复肠道屏障从而干预肠易激综合征。

Objective To explore the molecular mechanism of comprehensive treatment of irritable bowel syndrome(IBS)from the perspective of alleviating gastrointestinal symptoms and neuropsychiatric symptoms by using network pharmacology and molecular docking.Methods To retrieve the TCMSP database to obtaine the main active ingredients and the targets of Sini Powder,and the target genes of IBS were screened out through GeneCards and TTD databases.Then use STRING database and Cytoscape software to construct protein interaction network and screen the core genes,verifying the molecular docking of the core targets-drug component based on CB-Dock online molecular docking tool.Finally,used DAVID and Metascape databases respectively to conduct GO and KEGG pathways analysis.Results There were 112 active ingredients of Sini Powder and 204 effective targets,2805 IBS-related genes,and 152 targets in total,which mainly concerning IL-17 signaling pathway,VEGF signaling pathway,NF-κB signaling pathway,dopaminergic synaptic pathway,serotonin synaptic pathway and calcium signaling pathway.Conclusion Sini Powder could treat IBS by regulating neuroendocrine pathway,immune balance,improving mild intestinal inflammation and repairing intestinal barrier through multi-component,multi-path and multi-target ways.