基于网络药理学与分子对接探讨赤茵合剂治疗淤胆型肝炎的作用机制

Exploration of the mechanism of Chiyin Mixture in treating cholestatic hepatitis based on network pharmacology and molecular docking

目的:根据网络药理学及分子对接技术探讨赤茵合剂治疗淤胆型肝炎的作用机制。方法:通过TCMSP平台获得赤茵合剂有效成分及对应靶点,利用GeneCards及OMIM数据库获得淤胆型肝炎的疾病靶点,根据STRING数据库及Cytospace 3.0.1软件构建有效成分-疾病交集靶点蛋白质相互作用网络,DAVID数据库进行GO功能及KEGG通路富集分析,运用TCMSP、PubChem、UniProt、PDB平台及Chem 3D软件获得受体、配体3D结构,利用AutoDock Vina及PyMoL软件对其进行分子对接及可视化分析。结果:赤茵合剂靶点365个,淤胆型肝炎靶点255个,两者交集靶点18个。GO功能分析发现其作用机制可能与外源性刺激反应、基因表达正调控、相同蛋白结合等31种生物过程,细胞外空间、质膜、质膜的组成部分等17种细胞组分,蛋白结合、相同蛋白结合、酶结合等38种分子功能密切相关。KEGG通路富集分析发现其与NF-κB信号通路、Toll样受体信号通路、PI3K/Akt信号通路联系紧密。分子对接显示RAF1可能是赤茵合剂治疗淤胆型肝炎的重要靶点。结论:中药复方具有多成分、多靶点、多途径的治疗作用,赤茵合剂可能通过抗炎、抗氧化等机制治疗淤胆型肝炎。

Objective:To explore the mechanism of Chiyin Mixture in treating cholestatic hepatitis based on network pharmacology and molecular docking.Methods:The effective components and corresponding targets of Chiyin Mixture were obtained by TCMSP platform,and the disease targets of cholestatic hepatitis were obtained by GeneCards and OMIM database.According to the STRING database and Cytospace 3.0.1 software,the effective component-disease intersection target protein interaction network was constructed.The GO function and KEGG pathway enrichment were analyzed in the DAVID database.TCMSP,PubChem,UniProt,PDB platform and Chem 3D software were used to obtain the 3D structure of receptors and ligands,and AutoDock Vina and PyMoL software were used to perform molecular docking and visual analysis.Results:There were 365 targets of Chiyin Mixture,255 targets of cholestatic hepatitis,and 18 targets of their intersection.The functional analysis of GO showed that its mechanism of action may be closely related to 31 biological processes such as exogenous stimulus response,positive regulation of gene expression,and identical protein binding,17 cellular components such as extracellular space,plasma membrane,and components of the plasma membrane,and 38 molecular functions such as protein binding,identical protein binding,and enzyme binding.Enrichment analysis of KEGG pathway showed that it was closely related to NF-κB signaling pathway,Toll-like receptor signaling pathway and PI3K/Akt signaling pathway.Molecular docking showed that RAF1 might be an important target of Chiyin Mixture for the treatment of cholestatic hepatitis.Conclusion:Traditional Chinese medicine compound has multi-component,multi-target and multi-pathway therapeutic effects.Chiyin Mixture may treat cholestatic hepatitis through anti-inflammatory and antioxidant mechanisms.