基于网络药理学及分子对接探讨“金银花-黄芩”治疗病毒性心肌炎的作用机制

Mechanism of Jinyinhua(Lonicerae Japonicae Flos)-Huangqi(Scutellariae Radix)Herb Pair Therapy for Viral Myocarditis Based on Network Pharmacology and Molecular Docking Technology

目的基于网络药理学及分子对接技术探讨金银花-黄芩药对治疗病毒性心肌炎(VMC)的作用机制。方法利用TCMSP数据库筛选出金银花、黄芩的相关活性成分及靶点信息,通过Genecards及Disgenet查找病毒性心肌炎的潜在靶点。借助Venny图找出药物与疾病的交集靶点,运用String构建蛋白互作网络,将蛋白互作信息导入Cytoscape,借助cytohubba及MCODE插件筛选出核心靶点,利用Metascape对靶点进行GO和KEGG富集数据收集。PubChem数据库下载相关活性成分结构,利用AutodockTools 1.5.6软件对化合物及靶点分别进行加氢、去水、计算电荷等处理,通过Autodock Vina 1.1.2及PyMOL软件对关键成分和靶点进行分子对接及可视化分析。结果得到金银花-黄芩药对潜在56个活性成分及240个作用靶点,其中治疗VCM的核心靶点有16个,靶点主要参与RNA聚合酶Ⅱ启动子转录的正调控、炎性反应、缺氧、细胞对脂多糖的反应、凋亡、对抗生素的反应、细胞对有机化合物的反应等生物学过程,涉及KEGG相关富集通路91条,GO生物过程富集条目164条,GO细胞功能富集条目25条,GO细胞组分富集条目9条。分子对接显示关键成分与对应靶点具有较好的结合亲和力。结论金银花-黄芩药对通过“多靶点-多途径-多通路”治疗VMC,该研究为进一步阐述其抗病毒机制提供了理论依据。

Objective To investigate the mechanism of Jinyinhua(Lonicerae Japonicae Flos)-Huangqi(Scutellariae Radix)in treatment of viral myocarditis(VMC)based on network pharmacology and molecular docking technology.Methods Active components and targets of Jinyinhua(Lonicerae Japonicae Flos)and Huangqi(Scutellariae Radix)were screened by TCMSP database.The potential targets of viral myocarditis were identified by Genecards and Disgenet.Venny graph was used to find out the intersection targets of drugs and diseases.The protein interaction network was constructed by String and the protein interaction information was imported into Cytoscape.The core targets were screened by Cytohubba and Mcode plug-in and GO analysis and KEGG enrichment analysis of the targets was performed by Metascape.The structures of active components were downloaded from PubChem database and the compounds and targets were hydrogenated,dewatered and charged by AutodockTools 1.5.6 by using Autodock Vina 1.1.2 and PyMOL software.The molecular docking and visual analysis of key components and targets were carried out.Results Jinyinhua(Lonicerae Japonicae Flos)-Huangqi(Scutellariae Radix)was screened to have 56 potential active components and 240 targets,among which 16 were the core targets for VCM.The target sites were involved in such biological processes as positive regulation of RNA polymerase Ⅱ promoter transcription,inflammatory response,hypoxia,cellular response to lipopolysaccharide,apoptosis,antibiotic response and cellular response to organic compounds.There were 91 KEGG-related enrichment pathways,164 entries for GO biological process enrichment,25 entries for GO cell function enrichment,and 9 entries for GO cell component enrichment.Molecular docking showed that the key components had good binding affinity with the corresponding target.Conclusion Jinyinhua(Lonicerae Japonicae Flos)-Huangqi(Scutellariae Radix)can be used to treat VMC through“multi-target-multi-pathway-multi-pathway”.This study provided a theoretical basis for further elucidating its antiviral mechanism.