基于网络药理学及分子对接探讨肠复安治疗腹泻型肠易激综合征的机制研究

Exploring the action mechanism of the Changfuan decoction in the treatment of diarrheal irritable bowel syndrome based on network pharmacology and molecular docking

目的:基于网络药理学方法探讨肠复安汤治疗腹泻型肠易激综合征(Diarrhea-predominant Irritable Bowel Syndrome,IBS-D)的潜在作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库筛选肠复安汤所有药物的有效成分、作用靶点。借助Cytoscape 3.7.2构建“药物—成分—靶点”可视化网络。通过GeneCards、OMIM数据库筛选与IBS-D有关的疾病靶点。将疾病靶点与药物成分靶点的交集靶点导入STRING平台,构建药物-疾病靶点交互网络。通过Metascape数据库对关键靶点蛋白进行基因本体论(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。结果:肠复安汤共有162种活性化合物,对应268个疾病靶点。IBS-D疾病靶点有2559个。两者取交集获得186个交集靶点。“药物-有效成分-靶点”网络显示槲皮素、山柰酚、柚皮素、异鼠李素、木犀草素、汉黄芩素、β-谷甾醇、芒柄花素、豆甾醇等是肠复安汤治疗IBS-D的主要物质成分。根据蛋白质-蛋白质相互作用网络筛选出肠复安汤干预IBS-D的核心靶点,主要涉及丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6、肿瘤蛋白p53(Tumor Protein p53,TP53)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、JUN原癌基因、半胱氨酸蛋白酶3、IL-1B、雌激素受体1(Estrogen Receptor 1,ESR1)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、信号转导和转录活化因子3(Signal Transducer and Activator of Transcription 3,STAT3)、环氧化酶2(Prostaglandin-endoperoxide Synthase 2,PTGS2)、缺氧诱导因子1,α亚基、基质金属蛋白酶9(Matrix Metallopeptidase 9,MMP9)、丝裂原活化蛋白激酶3(Mitogen Activated Protein Kinase 3,MAPK3)等。KEGG富集分析显示肠复安汤治疗IBS-D的信号通路主要涉及TNF信号通路、细胞凋亡、TP53信号通路、核因子-κB(Nuclear Factor-κB,NF-κB)信号通路、T细胞受体信号通路、Jak-STAT信号通路等。结论:结果显示:肠复安汤治疗IBS-D是多成分、多靶点、多途径相互作用的结果,为进一步研究肠复安汤的作用机制及IBS-D相关疾病的基础或临床研究提供了一定的理论依据。

Objective:To explore the potential action mechanism of the Changfuan decoction(肠复安汤)in the treatment of IBS-D based on the method of network pharmacology.Methods:The active ingredients and action targets of all medicines in the Changfuan decoction were screened out by TCMSP database.The“medicine-component-target”visualization network was constructed by Cytoscape 3.7.2.The disease targets related to IBS-D were screened out by GeneCards and OMIM databases.The intersection targets of disease targets and medicine component targets were imported into STRING platform to build a“medicine-disease”targets interaction network.The GO enrichment analysis and KEGG pathway enrichment analysis of key target proteins were performed by Metascape database.Results:There were 162 active compounds in the Changfuan decoction,corresponding to 268 disease targets.There are 2559 disease targets of IBS-D.Taking the intersection of the two above,there were 186 intersecting targets.The“medicine-active component-target”network showed that quercetin,kaempferol,naringenin,isorhamnetin,lignan,baicalin,β-sitosterol,formononetin,and dousterol were the main components of the Changfuan decoction in the treatment of IBS-D.The core targets of the Changfuan decoction on IBS-D were screened according to the PPI network,mainly involving AKT1,TNF,IL-6,TP53,VEGFA,JUN,CASP3,IL-1B,ESR1,EGFR,STAT3,PTGS2,HIF1A,MMP9,MAPK3 and so on.The KEGG enrichment analysis showed that the signaling pathways of the Changfuan decoction in the treatment of IBS-D were mainly TNF signaling pathway,apoptosis,p53 signaling pathway,NF-κB signaling pathway,T cell receptor signaling pathway,Jak-STAT signaling pathway,etc..Conclusion:The treatment of IBS-D with the Changfuan decoction is the result of multi-component,multi-target and multi-pathway interaction,which provides a certain theoretical basis for further research on the action mechanism of the Changfuan decoction and the basic or clinical research on IBS-D related diseases.