基于整合网络毒理学和分子对接的雷公藤致肝毒性机制探讨  

Mechanism of hepatotoxicity caused by tripterygium wilfordii based on integrated network toxicology and molecular docking

作　　者：张丛惠 鞠建峰[1] 赵金娟[1] 朱日然[1] ZHANG Conghui;JU Jianfeng;ZHAO Jinjuan;ZHU Riran(Pharmaceutical Department,The Affliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250014,China)

机构地区：[1]山东中医药大学附属医院药学部,山东济南250014

出　　处：《安徽医药》2025年第3期501-506,I0002,共7页Anhui Medical and Pharmaceutical Journal

基　　金：山东省药品化妆品不良反应监测哨点课题项目(2022SDADRKY12);山东中医药学会临床药学科研专项基金项目(SDACM202203)。

摘　　要：目的基于网络毒理学和分子对接技术,对雷公藤有效成分中可能引起肝毒性的化合物进行预测及机制探讨。方法2023年1—2月,借助中药系统药理数据库和分析平台(TCMSP)、Swiss Target Prediction数据库获取雷公藤活性成分对应靶点,运用CTD、Genecards、OMIM等数据库获取肝毒性的相关基因靶点,将活性成分对应靶点与肝毒性相关基因靶点取交集,得到候选靶点。通过String平台对得到的候选靶点构建蛋白质相互作用(PPI)网络,挖掘网络中核心功能模块。基于Metascape平台,对候选靶点进行基因本体(GO)、京都基因和基因组数据库(KEGG)富集分析,并通过CytoScape 3.9.0软件构建雷公藤活性成分-肝毒性靶点-通路网络,进行网络拓扑分析,筛选核心成分与靶点。结果得到145个雷公藤主要成分产生肝毒性的候选靶点,通路富集结果显示雷公藤产生肝毒性可能与癌症途径、乙型肝炎、细胞凋亡等通路密切相关;雷公藤产生肝毒性的核心成分有雷公藤内酯甲、雷公藤内酯酮、雷公藤甲素,核心靶点有RELA、PIK3CG、PTGS2等。结论应用网络毒理学的方法,发现雷公藤中的多种活性成分可能通过多个靶点与多条信号通路产生肝毒性。Objective To predict the possible hepatotoxic compounds in the active components of Tripterygium wilfordii and to explore the mechansim based on the network toxicology and molecular docking technology.Methods From January to February 2023,pharmacology database and analysis platform of TCM system(TCMSP)and Swiss Target Prediction databases were used to obtain the corresponding targets of the active ingredients of Tripterygium wilfordii.CTD,Genecards,OMIM and other databases were used to obtain the gene targets related to liver toxicity.The corresponding targets of the active ingredients and the gene targets related to liver toxicity were intercrossed to obtain the candidate targets.The String platform was used to construct the protein-protein interaction(PPI)network for the candidate targets,and the core functional modules in the network were mined.Based on the Metascape platform,gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis of the candidate targets were performed,and CytoScape3.9.0 software was used to construct the active ingredients-hepatotoxic target-pathway network of Tripterygium wilfordii.The network topology analysis was performed to screen the core ingredients and targets.Results A total of 145 candidate targets of Tripterygium wilfordii's main ingredients causing hepatotoxicity were obtained.Pathway enrichment results showed that Tripterygium wilfordii's hepatotoxicity might be closely related to cancer pathway,hepatitis B,apoptosis and other pathways.The core components of Tripterygium wilfordii causing hepatotoxicity included triptolide A,triptolide one,and triptolide,and the core targets included RELA,PIK3CG,PTGS2,etc.Conclusion With network toxicology,it was found that various active components of Tripterygium wilfordii may produce hepatotoxicity through multiple targets and multiple signaling pathways.

关 键 词：雷公藤 肝毒性 网络毒理学 分子对接 靶点 

分 类 号：R285.1[医药卫生—中药学]