基于网络药理学探讨补骨脂潜在肝毒性机制

doi:10.19803/j.1672-8629.2020.12.01

摘要/Abstract

摘要： 目的采用网络毒理学和分子对接方法探讨补骨脂肝毒性作用机制。方法系统检索补骨脂文献,借助比较毒物基因组学数据库(CTD)和admetSAR数据库筛选毒性成分,通过Pharmmapper 服务器和GeneCards数据库预测潜在肝毒性靶点,进而使用Cytoscape 软件构建毒性成分-靶点互作网络,并利用SYBYL软件对hub靶点与毒性成分的结合进行分子对接验证,最后通过Metascape平台进行基因本体(GO)富集分析及基因组百科全书(KEGG)通路分析。结果补骨脂中筛选得到14个毒性成分,涉及242个肝毒性作用靶点;分子对接研究证实补骨脂毒性成分与10个hub靶点有着较好的结合活性;网络分析结果表明补骨脂肝毒性靶点主要与刺激反应、激酶活性、脂质结合、肽反应和辅因子代谢过程等生物过程及癌症通路、胰岛素信号通路、化学致癌、PPAR信号通路、HIF-1信号通路和Th17细胞分化等信号通路密切相关。结论利用中药多成分-多靶点-多通路的特点,探究了补骨脂肝毒性潜在作用机制,为后续进一步深入验证补骨脂肝毒性作用机制研究提供新思路。

关键词: 网络毒理学, 补骨脂, 肝毒性, 分子对接

Abstract: Objective To explore the mechanism of Psoralea corylifolia L. hepatotoxicity using network toxicology and molecular docking.Methods Literature on Psoralea Corylifolia L. was systematically retrieved, toxic components were screened by means of comparative toxicology genomics database (CTD) and admetSAR database, Psoralea Corylifolia targets were predicted by Pharmmapper server and GeneCards database before a toxic component-target interaction network was constructed by using Cytoscape software. Molecular docking validation was carried out on the binding of hub targets and toxic components by using SYBYL software, and finally GO biological function and KEGG pathway enrichment analysis was carried out by using the Metascape platform.Results Fourteen toxic components were screened from Psoralea Corylifolia L., involving 242 hepatotoxic targets. Molecular docking studies confirmed that the toxic components of Psoralea corylifolia L. had good binding activity to 10 hub targets. The results of network analysis showed that hepatotoxic targets of Psoralea Corylifolia L. were mainly related to such biological processes as cellular response to hormone stimuli, kinase activity, lipid binding and response peptide, cofactor metabolic process and to such signaling pathways as pathways in cancer, insulin signaling pathway, chemical carcinogenesis, PPAR signaling pathway, HIF-1 signaling pathway and Th17 cell differentiation.Conclusion The potential mechanism of Psoralea Corylifolia L. hepatotoxicity has been explored based on the multi-component, multi-target, and multi-pathway characteristics of traditional Chinese medicine, which brings new ideas for further research on the mechanism of Psoralea Corylifolia L. hepatotoxicity.

Key words: network toxicology, Psoralea Corylifolia L., hepatotoxicity, molecular docking

中图分类号:

R968

刘伟, 秦柯, 张彦忠, 白素平. 基于网络药理学探讨补骨脂潜在肝毒性机制[J]. 中国药物警戒, 2020, 17(12): 849-855.

LIU Wei, QIN Ke, ZHANG Yanzhong, BAI Suping. Mechanism of Potential Hepatotoxicity of Psoralea Corylifolia L. Based on Network Toxicology Analysis[J]. Chinese Journal of Pharmacovigilance, 2020, 17(12): 849-855.

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