基于网络药理学与分子对接探讨黄连解毒汤治疗白念珠菌感染的作用机制

Study on the mechanism of Huanglian Jiedu decoction in the treatment of Candida albicans infection based on network pharmacology and molecular docking

目的运用网络药理学与分子对接探讨黄连解毒汤治疗白念珠菌感染的作用机制,为临床应用和基础研究提供理论依据。方法运用TCMSP和BATMAN-TCM数据库检索黄连解毒汤的有效成分及作用靶点,通过GeneCards、OMIM、PharmGkb、TTD、DrugBank数据库收集疾病相关靶点。运用Cytoscape 3.8.0软件构建“活性成分-靶点”网络,借助STRING平台构建交集蛋白互作网络,并使用Cytoscape对网络进行拓扑分析,获取核心靶点,通过R语言进行GO富集分析和KEGG通路富集分析,最后将主要活性成分与核心靶点进行分子对接验证。结果黄连解毒汤治疗白念珠菌感染的活性成分有槲皮素、山柰酚、汉黄芩素、黄芩新素等,核心靶点为HIF1A、MMP9、AKT1、FN1、PTGS2、IFNG、IL1B、STAT1、CASP8。富集得到IL-17信号通路、Th17细胞分化、Toll样受体信号通路等,主要通过调节炎症反应和细胞免疫等生物过程发挥治疗作用。分子对接结果表明,主要活性成分与核心靶点具有较强的结合能。结论黄连解毒汤能通过多成分-多靶点-多途径共同治疗白念珠菌感染,为临床应用及基础研究提供理论基础和参考依据。

Objective To explore the mechanism of action of Huanglian Jiedu decoction in the treatment of Candida albicans infection by network pharmacology and molecular docking,and to provide theoretical basis for clinical application and basic research.Methods TCMSP and BATMAN-TCM databases were used to search the effective components and targets of Huanglian Jiexing decoction,and disease-related targets were collected through GeneCards,OMIM,PharmGkb,TTD and DrugBank databases.The‘active ingredient-target’network was constructed by Cytoscape 3.8.0 software,and the intersecting protein interaction(PPI)network was constructed by STRING platform.Cytoscape was used to analyze the network topology and obtain the core targets.GO enrichment and KEGG pathway enrichment analysis were carried out by R language.Finally,the main active ingredients were verified by molecular docking with the core targets.Results The active components of Huanglian Jiedu decoction in the treatment of Candida albicans infection were quercetin,kaempferol,wogonin and neobaicalein,and the core targets were HIF1A,MMP9,AKT1,FN1,PTGS2,IFNG,IL1B,STAT1 and CASP8.The enrichment yielded IL-17 signalling pathway,Th17 cell differentiation and Toll-like receptor signalling pathway,which mainly exert therapeutic effects through regulating biological processes such as inflammatory response and cellular immunity.The molecular docking results showed that the main active components have strong binding energy with the core targets.Conclusion Huanglian Jiedu decoction can treat Candida albicans infection through multiple components,targets and pathways,providing theoretical basis and reference for clinical application and basic research.