基于网络药理学与分子对接探讨二妙散治疗宫颈人乳头瘤病毒感染的作用机制

Mechanism of Ermiao Powder in treating cervical HPV infection based on network pharmacology and molecular docking

目的 基于网络药理学和分子对接探讨二妙散治疗宫颈人乳头瘤病毒(HPV)感染作用机制。方法 通过中药系统药理学数据库与分析平台检索二妙散的有效成分和作用靶点;GeneCards、OMIM数据库检索宫颈HPV感染相关疾病靶点。将药物有效成分作用靶点与疾病靶点取交集;利用STRING数据库构建交集靶点的蛋白相互作用(PPI)网络,利用Cytoscape3.8.2软件对PPI进行拓扑分析;将潜在作用靶点导入DAVID数据库进行基因本体功能(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;利用AutoDock Tools 1.5.7软件和Pymol软件对核心作用靶点与有效成分进行分子对接及可视化。结果 获得二妙散有效成分28个,作用靶点为221个,筛选出核心靶点5个,包括蛋白激酶B1(Akt1)、肿瘤蛋白p53(TP53)、雌激素受体α(ESR1)、转录因子AP-1(JUN)、半胱氨酸天冬氨酸蛋白酶3(CASP3)。GO富集分析显示,潜在作用靶点与细胞增殖的正向调节、细胞凋亡过程的负调控、转录的正调控、RNA聚合酶II启动子转录的正调控等生物过程有关;KEGG富集分析结果包括磷脂酰肌醇3-激酶(PI3K)/Akt信号通路、白细胞介素-17(IL-17)信号通路、细胞衰老、肿瘤坏死因子(TNF)信号通路等,核心作用靶点与有效成分具有较稳定的结合能力。结论 二妙散具有多种活性成分,通过多靶点、多途径干预宫颈HPV感染,发挥治疗作用。

Objective To explore the mechanism of Ermiao Powder in treating cervical HPV infection based on network pharmacology and molecular docking.Method The active components and targets of Ermiao Powder were searched through the pharmacology database and analysis platform of TCM system.GeneCards and OMIM databases search for cervical HPV infection related disease targets.The target of drug active ingredient is intersected with the target of disease.The protein interaction(PPI)network of intersecting targets was constructed using STRING database,and topological analysis of PPI was carried out by Cytoscape 3.8.2 software.Potential targets were imported into DAVID database for GO and KEGG pathway enrichment analysis.AutoDock Tools 1.5.7 software and Pymol software were used for molecular docking and visualization of the core target and the active component.Result 28 Effective ingredients were obtained from Ermiao Powder,with 221 target sites.Five core targets were screened,including Akt1,TP53,ESR1,JUN,and CASP3.GO enrichment analysis shows that potential targets are related to biological processes such as positive regulation of cell proliferation,negative regulation of cell apoptosis,positive regulation of transcription,and positive regulation of RNA polymerase II promoter transcription.The KEGG enrichment analysis results include the PI3K/Akt signaling pathway,IL-17 signaling pathway,cell aging,TNF signaling pathway,etc.The core target of action has relatively stable binding ability with active ingredients.Conclusion Ermiao Powder has multiple active ingredients that can intervene in cervical HPV infection through multiple targets and pathways,exerting therapeutic effects.