基于网络药理学吴茱萸致肝毒性机制研究

目的筛选吴茱萸主要肝毒性成分,预测毒性成分作用靶点,探讨其多成分-多靶点-多通路的肝毒性作用机制。方法依据TCMSP数据库、PubChem数据库Pharmmapper服务器、UniprotKB数据库筛选吴茱萸的活性成分,并预测肝毒性作用靶点。借助Cytoscape软件构建吴茱萸毒性成分-作用靶点网络,通过KOBAS3.0数据库对靶点基因功能及代谢通路进行分析。结果网络分析结果表明吴茱萸中筛选得到14-甲酰基二氢吴茱萸次碱、芳樟醇、1-甲基-2-戊烷基-4(1H)喹诺酮、辛弗林、柠檬烯等147个潜在毒性成分,涉及靶点F2、PIM1、MMP13、MAOB等49个,经建立网络连接,细胞代谢、催化活性、刺激反应等通路可能与肝毒性作用相关。结论应用网络药理学的方法,发现吴茱萸中的多种潜在毒性成分可能通过多个靶点与细胞代谢、催化活性等通路相互作用,从而可能产生肝毒性,为后续进一步深入验证吴茱萸肝毒性作用机制研究提供新线索。

Study on hepatotoxicity mechanism of Euodiae Fructus based on network pharmacology

Objective To screen the main hepatotoxic components, predict the target of active components, and explore the mechanism of liver toxicity of Euodiae Fructus (EF). Methods According to TCMSP database, PubChem database Pharmmapper server and Uniprot KB database information, active constituents of EF were screened, and targets of hepatotoxicity were predicted. The active component-acting target network of EF was constructed by Cytoscape software, while the function and metabolic pathways of target genes were analyzed by KOBAS 3.0 database. Results Network analysis results demonstrated that 147 potential hepatotoxic components from EF, accompanied with 49 targets like F2, PIM1, MMP13 and MAOB, connecting with cell metabolism, catalytic activity, stimulate the reaction pathways may be associated with EF''s liver toxic effects. Conclusion Based on network pharmacology methodology, this paper disclosed that many potential toxic components in EF may interact with cell metabolism, catalytic activity and other pathways through multiple targets, leading to produce hepatotoxicity in vivo as a result, which can provide new clues for further researches of the hepatotoxicity mechanism study of EF.