基于网络药理学及分子对接研究柴胡-黄芩药对治疗乙型病毒性肝炎作用机制

Approaches of Network Pharmacology and Molecular Docking to Uncover the Mechanism of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)for the Treatment of Hepatitis

目的乙型病毒性肝炎目前仍是全球主要公共卫生问题之一。该研究通过网络药理学方法及分子对接,对柴胡-黄芩治疗乙型病毒性肝炎的主要活性成分及其潜在作用机制进行探讨。方法选择应用TCMSP等数据库,并对柴胡-黄芩的化学成分进行收集,得出其中的有效活性成分,之后推测出其作用靶点。利用GeneCards数据库,对乙型病毒性肝炎的相关基因进行收集,在Cytoscape软件的条件下,制作出药物-靶点和疾病-靶点的PPI图。通过对关键靶点基因进行分析后,建立PPI网络图,以关键靶点蛋白为基础,实现GO及KEGG通路富集分析。结果收集的柴胡-黄芩和乙型病毒性肝炎的交集靶点共计达到了75个。蛋白互作网络发现IL6、CASP3、VEGFA、EGFR、MAPK8、MYC、ESR1等可能是柴胡-黄芩治疗乙型病毒性肝炎的关键靶点。利用GO通路功能注释和KEGG富集分析,探讨其治疗乙型病毒性肝炎的功能富集分析及通路富集分析。分子对接结果显示槲皮素(quercetin)和IL6能稳定地结合并通过氨基酸残基GLU42、GLU106、ARG104和ASP160等发生相互作用。结论柴胡-黄芩对治疗乙型病毒性肝炎具有多途径、多靶点作用的特点,初步揭示了其作用的关键靶点及涉及的生物学过程和信号通路,为后续研究该药对提供参考和依据。

Objective Viral hepatitis B is still one of the major public health problems in the world.In this study,the main active ingredients of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)in the treatment of hepatitis and their potential mechanism were discussed by means of network pharmacology and molecular docking.Methods Databases,including TCMSP,were utilized for the analysis of chemical ingredients of the drug pair.The active components were screened and the corresponding functional targets were traced.By GeneCards database,genes correlating with hepatitis were attained.Visualized networks of drug-target and disease-target were plotted by Cytoscape software.As the core target genes underwent examinations,the protein-protein interaction(PPI)network was established,then enrichment analysis of GO and KEGG pathways based on key target proteins.Finally,the key active ingredients were docked with the selected functional targets by Autodock.Results A total of 75 intersecting targets of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)and hepatitis were collected.The protein interaction network found that IL6,CASP3,VEGFA,EGFR,MAPK8,MYC and ESR1 may be the key targets of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)in the treatment of hepatitis.The functional enrichment analysis and pathway enrichment analysis of GO and KEGG pathways in the treatment of hepatitis were explored by means of functional annotation and enrichment analysis of GO and KEGG pathways.Molecular docking results showed that quercetin and IL6 could bind stably and interact through amino acid residues GLU42,GLU106,ARG104 and ASP160.Conclusion Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)has the characteristics of multi-pathway and multi-target in the treatment of hepatitis.The key targets of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)and their biological processes and signal pathways are preliminarily revealed,which can provide reference and basis for the follow-up study of this traditional Chinese medicine.