基于网络药理学和分子对接探究肠炎宁颗粒治疗功能性腹泻和腹泻型肠易激综合征的作用机制  

Mechanism of Changyanning Granules in treatment of functional diarrhea and diarrhea irritable bowel syndrome based on network pharmacology and molecular docking

作　　者：田文国 陈金鹏 王春芳 刘毅[2,3,4] 盖晓红 刘全国[5] 田成旺 陈常青 TIAN Wen-guo;CHEN Jin-peng;WANG Chun-fang;LIU Yi;GAI Xiao-hong;LIU Quan-guo;TIAN Cheng-wang;CHEN Chang-qing(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;Tianjin Key Laboratory of Quality Marker of Traditional Medicine,Tianjin 300462,China;State Key Laboratory of Drug Delivery and Pharmacokinetics,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;Hainan Huluwa Pharmaceutical Group Co.,Ltd.,Haikou 570216,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津药物研究院,天津300462 [3]天津市中药质量标志物重点实验室,天津300462 [4]释药技术与药代动力学国家重点实验室,天津300462 [5]海南葫芦娃药业集团股份有限公司,海南海口570216

出　　处：《中草药》2022年第22期7135-7147,共13页Chinese Traditional and Herbal Drugs

基　　金：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)。

摘　　要：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Cytoscape 3.9.1软件获取核心靶点;OmicsBean数据库对核心靶点进行基因本体(gene ontology,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;Schr?dinger-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 metalloproteinase 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 protein-protein 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 rea

关 键 词：肠炎宁颗粒 功能性腹泻 腹泻型肠易激综合征 网络药理学 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 

分 类 号：R285.5[医药卫生—中药学]