摘要
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。
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.
作者
郑罗棋
惠慧
田港
徐晓芬
秦路平
单琪媛
ZHENG Luo-qi;HUI Hui;TIAN Gang;XU Xiao-fen;QIN Lu-ping;SHAN Qi-yuan(School of Pharmaceutical Science,Zhejiang Chinese Meidical University,Hangzhou 311402,China)
出处
《中草药》
CAS
CSCD
北大核心
2020年第2期419-425,共7页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金青年基金项目(81703707)
浙江省中医药科技计划项目(2019ZA038)
国家留学基金项目(CSC No.201908330362).
关键词
吴茱萸
肝毒性
网络药理学
毒性机制预测
细胞代谢
Euodiae Fructus
hepatotoxicity
network pharmacology
prediction of toxic mechanism
cell metabolism
