基于网络药理学方法的雷公藤药理、毒理机制研究

Based on Network Pharmacological Approaches to Re-study the Pharmacology and Toxicity Mechanism of Tripterygium Wilfordii Hook F.

目的应用网络药理学方法对雷公藤可能的药理及毒理机制进行再研究,为该药物的合理使用和深度研发提供新的研究策略。方法借助多个在线数据库资源(SinoMed,Polysearch,DrugBank,David),挖掘雷公藤中已知化合物的生物学信息,筛选相似药物及与雷公藤相关性高的疾病,获取高相似度药物的编号和高相关性疾病的对应靶标,构建雷公藤化合物靶标"蛋白-蛋白"相互作用(PPI)网络及"在靶、脱靶"相关分子网络。结果除已知的抗类风湿等药理作用外,雷公藤各组分具有潜在的抗肿瘤、抗氧化等活性;雷公藤化合物在靶效应主要与机体的免疫调节功能有关,脱靶效应则参与细胞增殖、凋亡、炎症反应等重要生物化学反应过程,间接提示雷公藤的脱靶效应可能对应其副反应(毒性)。结论网络药理学研究方法从系统、非线性层面挖掘雷公藤既有知识之间的联系,通过分析对应靶标间相互关系及直接作用模式,揭示潜在的抗肿瘤、抗氧化等活性,为其相应的分子药理机制研究提供新的方向。

Objective Using network pharmacology methods,the pharmacological and toxicological mechanisms of Tripterygium Wilfordii Hook F.were restudied for providing some new data and research strategy on its development and application.Methods The protein-protein interaction networks of drug targets,the on-target and off-target related networks were built by using some online database（SinoMed,Polysearch,DrugBank,David etc.）.The biological information,pathways,and functions were obtained by network analysis.Results Besides anti-rheumatoid,the active pharmaceutical ingredients of Tripterygium Wilfordii Hook F.showed anti-tumor,anti-oxidation.The on-target effect of Tripterygium Wilfordii Hook F.was related to regulate immune function.Taking part in process of cell proliferation,apoptosis and inflammation,the off-target effect of Tripterygium Wilfordii Hook F.has been indirectly suggesting the relationship with its side effects.Conclusions The network pharmacology method explores the connection between the existing knowledge of Tripterygium Wilfordii from the system and nonlinear levels,and analyzes the relationship between the corresponding targets and the direct-action model to reveal the potential anti-tumor and anti-oxidation activities for their corresponding molecules.The study of network pharmacological provides a new mechanism research direction.