目的 运用网络药理学和分子对接方法探究肠炎宁颗粒治疗功能性腹泻(functional diarrhea,FD)和腹泻型肠易激综合征(diarrhea irritable bowel syndrome,IBS-D)的作用机制。方法 通过TCMSP数据库、文献检索肠炎宁颗粒5味药材的成分;SwissADME平台筛选肠炎宁颗粒活性成分;SwissTargetPrediction平台反向靶标预测肠炎宁颗粒活性成分作用靶点;GeneCards数据库预测FD和IBS-D靶点;Venny 2.1.0获取肠炎宁颗粒治疗FD和IBS-D的交集靶点;STRING数据库获取蛋白质相互作用(protein-protein interaction,PPI)网络后导入Cytoscape3.9.1软件获取核心靶点;OmicsBean数据库对核心靶点进行基因本体(geneontology,GO)功能和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;Cytoscape 3.9.1软件构建"药材-活性成分-靶点"及"关键活性成分-核心靶点-通路"网络;Schrödinger-Maestro对关键活性成分和核心靶点进行分子对接。结果 从肠炎宁颗粒中筛选得到治疗FD和IBS-D的活性成分30个,其中10个关键活性成分为甲基异茜草素、槲皮素、4',5-二羟基黄酮、山柰酚、鞣花酸、焦性没食子酸、金圣草黄素、咖啡酸、木犀草素、芹菜素;24个核心靶点为蛋白激酶B1(protein kinase B1,AKT1)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、基质金属蛋白酶2(matrix metal loproteinase 2,MMP2)、MMP9等。KEGG通路富集分析发现其主要涉及内分泌抵抗、磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路、前列腺癌等通路。分子对接表明关键活性成分与核心靶点均可自发结合。结论 肠炎宁颗粒可能通过多成分、多靶点和多通路,降低内脏敏感、减少炎性反应、调节肠道菌群,从而治疗FD和IBS-D。

Objective To explore the mechanism of Changyanning Granules (肠炎宁颗粒) in treatment of functional diarrhea (FD) and diarrhea irritable bowel syndrome (IBS-D) by using network pharmacology and molecular docking. Methods The ingredients of five medicinal materials from Changyanning Granules were searched by TCMSP database and literature. SwissADME platform was used to screen the active ingredients of Changyanning Granules; SwissTargetPrediction platform was used to predict the targets of active ingredients of Changyanning Granules; GeneCards database was used to predict FD and IBS-D targets; Venny 2.1.0 was used to collect the intersection targets of Changyanning Granules in treating FD and IBS-D; STRING database was used to acquire proteinprotein interaction (PPI) network and then import into Cytoscape 3.9.1 software to acquire the core targets; OmicsBean database was used to carry out gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on core targets; “Medicinal material-active ingredient-target” and “key active ingredient-core target-pathway” networks were constructed by Cytoscape 3.9.1 software; Schrödinger-Maestro was used to perform molecular docking between key active components and core targets. Results Thirty active ingredients for treating FD and IBS-D were screened from Changyanning Granules, among which 10 key active ingredients were rubiadin, quercetin, 4',5-dihydroxyflavone, kaempferol, ellagic acid, pyrogallol, chrysoeriol, caffeic acid, luteolin and apigenin. 24 core targets were protein kinase B1 (AKT1), epidermal growth factor receptor (EGFR), matrix metalloproteinase 2 (MMP2), MMP9, etc. KEGG pathway enrichment analysis found that it mainly involved endocrine resistance, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, prostate cancer and other pathways. Molecular docking indicated that key active ingredients could spontaneously combine with core targets. Conclusion Changyanning Granules may reduce visceral sensitivity, reduce inflammatory reaction and regulate intestinal flora through multiple components, multiple targets and multiple pathways, so as to treat FD and IBS-D.

R285.5

中-德中药与植物药创新研发国际合作基地医药国际合作专项（0610-2140NF020630）