基于网络药理学和分子对接探讨四神丸治疗肠易激综合征的作用机制

Exploring The Mechanism of Action of Sishen Wan in Treating Irritable Bowel Syndrome Based on Network Pharmacology and Molecular Docking

目的:利用网络药理学技术和生物信息学方法探讨四神丸治疗肠易激综合征(irritable bowel syndrome,IBS)的活性成分、作用靶点及分子机制。方法:运用TCMSP、Pubchem、SEA、Swiss Target Prediction、GeneCards等数据库筛选四神丸活性成分、预测靶点及IBS疾病靶点;采用Cytoscape 3.7.2软件构建化合物-靶点-疾病网络和靶点蛋白相互作用网络;通过DAVID数据库进行基因本体功能富集分析和京都基因与基因组百科全书通路进行富集分析;利用AutoDock Tools软件进行活性成分和核心靶点的分子对接验证。结果:共筛选得到四神丸的活性成分18个,靶点693个,IBS相关疾病靶点422个,与四神丸的交集靶点共有82个;得出PPI网络的拓扑学分析结果,共筛选出20个关键靶点。GO富集条目644个,主要涉及炎症反应、平滑肌细胞增殖的正调控、蛋白激酶活性、MAP激酶活性的正调控、多巴胺分解代谢过程和白细胞介素-17产生的正调控等。KEGG通路显著富集148条,得出包括与IBS炎症与免疫相关通路、与细胞增殖与凋亡相关通路、与氧化应激和脂质过氧化相关通路等发挥治疗IBS作用的相关通路。分子对接结果显示芦丁、补骨脂酚、补骨脂甲素、金丝桃苷这4个活性成分能与IL1B、TLR4、IL6、TNF结合并形成较为稳定的构象。结论:网络药理学联用分子对接技术揭示四神丸可以通过多成分、多靶点、多途径治疗IBS。

Objective:To explore the active ingredients,targets,and molecular mechanisms of Sishen Wan in the treatment of irritable bowel syndrome(IBS)using network pharmacology techniques and bioinformatics methods.Methods:TCMSP,Pubchem,SEA,Swiss Target Prediction,GeneCards and other databases were used to screen the active ingredients,predicted targets and IBS disease targets of Sishen Wan;Construct compound target disease networks and target protein interaction networks using Cytoscape 3.7.2 software;Per-form gene ontology functional enrichment analysis through the DAVID database and enrichment analysis through the Kyoto Encyclope-dia of Genes and Genomes pathway;Use AutoDock Tools software for molecular docking validation of active ingredients and core tar-gets.Results:A total of 18 active ingredients,693 targets,422 IBS related disease targets,and 82 intersecting targets were screened from Sishen Wan;The topological analysis results of PPI network were obtained,and a total of 20 key targets were screened.There are 644 GO enriched entries,mainly involving positive regulation of inflammatory response,smooth muscle cell proliferation,protein kinase ac-tivity,positive regulation of MAP kinase activity,dopamine catabolism process,and positive regulation of interleukin-17 production.The KEGG pathway significantly enriched 148 pathways,including pathways related to IBS inflammation and immunity,pathways related to cell proliferation and apoptosis,pathways related to oxidative stress and lipid peroxidation,and other pathways that exert therapeutic ef-fects on IBS.The molecular docking results showed that the four active ingredients,rutin,psoralen,psoralen A,and hyperoside,can bind to IL1B,TLR4,IL6,and TNF and form relatively stable conformations.Conclusion:The combination of network pharmacology and mo-lecular docking technology reveals that Sishen Wan can treat IBS through multiple components,targets,and pathways.