目的:基于网络药理学方法和分子对接技术探讨消炎利胆片治疗急性胆囊炎的潜在作用机制.方法:采用中药系统药理学数据库与分析平台(TCMSP)、化学专业数据库及ETCM数据库检索获取消炎利胆片的化学成分,通过SwissADME数据库进一步筛选活性成分并导入SwissTargetPrediction数据库预测药物相关靶点.利用GeneCards数据库和OMIM数据库检索急性胆囊炎相关靶点,通过Venny 2.1在线平台获取"药物-疾病"交集靶点,并将"药物-疾病"共同靶点导入STRING数据库构建蛋白质-蛋白质相互作用网络.利用DAVID数据库对"药物-疾病"共同靶点进行基因本体论(GO)功能注释和京都基因与基因百科全书(KEGG)通路富集分析.运用Cytoscape软件构建"药物成分-靶点-信号通路"网络,计算网络拓扑学参数并筛选消炎利胆片发挥治疗急性胆囊炎作用的重要活性成分及核心靶点,通过AutoDock平台进行分子对接验证.结果:共获得44个消炎利胆片活性成分及186个药物相关靶点,获得823个急性胆囊炎潜在靶点,取交集后得到"药物-疾病"共同靶点33个,这些靶点主要涉及磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)及缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1等信号通路;"药物成分-靶点-通路"网络拓扑学分析提示槲皮素、异鼠李素、芹菜素、7-羟基香豆素和咖啡酸等可能是消炎利胆片发挥治疗急性胆囊炎作用的重要活性成分,关键靶点为表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、醇醛酮还原酶家族1成员B1(Aldo-Keto Reductase Family 1 Member B1,AKR1B1)、胰岛素样生长因子1受体(Insulin-like Growth Factor 1 Receptor,IGF1R)以及ATP结合家族亚家族G成员2(ATP Binding Cassette Sub-Family G Member 2,ABCG2)等;分子对接显示大部分核心靶点与活性成分有较高的结合活性.结论:本研究基于网络药理学方法及分子对接技术初步揭示消炎利胆片通过多成分、多靶点、多途径治疗急性胆囊炎的机制,为探索消炎利胆片的药理机制和合理临床应用提供了一定的参考.
A study on the mechanism of treating acute cholecystitis with the Xiaoyan Lidan tablets based on network pharmacology and molecular docking
Objective:To discuss the mechanism of the Xiaoyan Lidan tablets(消炎利胆片)in the treatment of acute cholecystitis based on network pharmacology method and molecular docking technology.Methods:The chemical composition of the Xiaoyan Lidan tablets was retrieved using the TCMSP database,the Chemistry database and the ETCM database,and then the active ingredients were further screened using the SwissADME database and imported into the SwissTargetPrediction database to predict drug-related targets.The targets related to acute cholecystitis were retrieved using GeneCards database and OMIM database.The drug-disease intersection targets were obtained through the Venny 2.1 online platform,and the drug-disease common targets were imported into the STRING database to build a protein-protein interaction(PPI)network.The DAVID database was used for gene ontology(GO)function annotation and Kyoto encyclopedia of genes and genes(KEGG)pathway enrichment analysis of drug-disease common targets.Cytoscape software was used to construct the component-target-pathway network,calculate network topology parameters and screen the important active ingredients and core targets of the Xiaoyan Lidan tablets for the treatment of acute cholecystitis.Molecular docking verification was carried out through the AutoDock platform.Results:A total of 44 active ingredients and 186 drug-related targets of the Xiaoyan Lidan tablets were obtained,and 823 potential targets for acute cholecystitis were obtained.A total of 33 drug-disease common targets were obtained after intersection,which mainly involved PI3K-Akt,MAPK and HIF-1 signaling pathways.The topological analysis of the component-target-pathway network suggested that quercetin,isorhamnetin,apigenin,umbelliferone and caffeic acid might be important active ingredients of the Xiaoyan Lidan tablets in the treatment of acute cholecystitis with EGFR,AKT1,AKR1B1,IGF1R and ABCG2 as the key targets.Molecular docking results showed that most core targets had high binding activity with active components.Conclusion:This study provides a preliminary insight into the mechanism of the Xiaoyan Lidan tablets in the treatment of acute cholecystitis through multi-component,multi-target and multi-pathway based on a network pharmacological approach and molecular docking technology,which provides a certain reference for exploring the pharmacological mechanism and rational clinical application of the Xiaoyan Lidan tablets.
The Xiaoyan Lidan tabletsAcute cholecystitisNetwork pharmacologyMolecular docking
万方数据
维普
