五灵胶囊治疗慢性乙型肝炎作用机制的网络药理学研究及分子对接验证

Network pharmacology research and molecular docking verification on the mechanism of Wuling Capsule in treating chronic hepatitis B

目的基于网络药理学方法和分子对接技术探究五灵胶囊治疗慢性乙型肝炎的作用机制。方法利用TCMSP数据库检索五灵胶囊的活性成分及作用靶点;通过OMIM和GeneCards数据库获取慢性乙型肝炎的相关靶点。筛选出药物与疾病的交集靶点,通过Cytoscape 3.7.2和STRING数据库分别构建“药物-活性成分-靶点”及蛋白相互作用网络并筛选出关键活性成分与核心靶点。运用DAVID数据库进行基因本体论功能富集分析(GO)和京都基因与基因组百科全书富集分析(KEGG),利用AutoDock Vina软件进行分子对接验证。结果共获得五灵胶囊活性成分102个,药物与疾病的交集靶点133个。其中,五灵胶囊治疗慢性乙型肝炎的关键活性成分为槲皮素、木犀草素、山奈酚、丹参酮ⅡA、异鼠李素等;核心靶点为胱天蛋白酶3(CASP3)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、TP53、白细胞介素-6(IL-6)、表皮生长因子(EGF)等。GO富集分析涉及433个生物学过程,40个细胞组分,80个分子功能。KEGG富集分析涉及白细胞介素-17(IL-17)信号通路、糖尿病并发症晚期糖基化终产物-晚期糖基化终产物受体(AGE-RAGE)信号通路、肿瘤坏死因子(TNF)信号通路等145条信号通路。分子对接显示关键活性成分与核心靶点之间有良好的结合活性。结论五灵胶囊可以通过多成分、多靶点、多途径发挥对慢性乙型肝炎的治疗作用,相关结果为后续研究和临床应用提供依据。

Objective To explore the mechanism of Wuling Capsule in the treatment of chronic hepatitis B based on network pharmacology and molecular docking.Methods The active ingredients and targets of Wuling Capsule were searched by TCMSP database;the relevant targets of chronic hepatitis B were obtained from GeneCards and OMIM database.Screening out the common targets of drug and disease,“drug-active ingredient-target”and protein-protein interaction network was constructed through Cytoscape 3.7.2 and STRING database respectively,then the key active ingredients and core targets were screened out.GO and KEGG analysis were carried out with the help of DAVID database,molecular docking verification was performed by using AutoDockTools software.Results A total of 102 active ingredients of Wuling Capsule were collected,133 common targets between drug and disease were obtained.Among them,the key active ingredients of Wuling Capsule in the treatment of chronic hepatitis B were quercetin,luteolin,kaempferol,tanshinone ⅡA,isorhamnetin,etc.The core targets were CASP3,AKT1,TP53,IL-6,EGF,etc.GO enrichment analysis involved 433 biological processes,40 cellular components and 80 molecular functions.KEGG analysis involved 145 signaling pathways,including IL-17 signaling pathway,AGE-RAGE signaling pathway in diabetic complications,TNF signaling pathway,etc.The molecular docking results showed that the key active ingredients exhibit good binding activity with core targets.Conclusion Wuling Capsule may exert therapeutic effect on chronic hepatitis B through multiple components,multiple targets and multiple pathways,providing a basis for subsequent research and clinical application.