基于网络药理学的雷公藤效毒作用机制研究

Pharmacodynamic effect and virulent effect of Tripterygium wilfordii based on network pharmacology

探讨有毒中药雷公藤中主要成分雷公藤甲素、雷公藤氯内酯醇、雷公藤红素、去甲泽拉木醛、雷公藤春碱、雷公藤新碱的效毒作用机制。采用admetSAR在线评估系统计算雷公藤主要成分的性质,通过多个数据库挖掘并收集成分的潜在靶点,经生物信息学数据库DAVID对潜在靶点进行通路富集。应用Cytoscape软件建立“靶点-通路”网络,并对网络进行拓扑分析。雷公藤主要化学成分均能透过血脑屏障,具有肠渗透性。共预测到靶点65个,富集通路涉及癌症信号通路(pathways in cancer)、乙肝(hepatitis B)、类风湿性关节炎(rheumatoid arthritis)、美洲锥虫病[chagas disease(American trypanosomiasis)]、Toll样受体信号通路(Toll-like receptor signaling pathway)、细胞凋亡(apoptosis)、结肠癌(colorectal cancer)、NF-κB信号通路(NF-kappa B signaling pathway)等。雷公藤主要通过调控炎症信号通路、癌症信号通路等发挥免疫性疾病及癌症的治疗作用,其毒性作用可能与细胞凋亡以及对药物代谢酶的作用有关。

To investigate the pharmacodynamic effect and virulent effect of the main components of the toxic Chinese medicine Tripterygium wilfordii,such as triptolide,tripchlorolide,tripterine,demethylzeylasteral,wilfotrine and euonine,the admetSAR online assessment system was used to calculate the properties of the main components of T.wilfordii.The potential targets of the components were mined and collected through multiple databases,and the potential targets were enriched by the bioinformatics database DAVID.Cytoscape software was used to establish a"target-pathway"network and perform topology analysis on the network.The main chemical components of T.wilfordii were able to penetrate the blood-brain barrier and had intestinal permeability.A total of 65 targets were pre-dicted,including pathways in cancer,hepatitis B,rheumatoid arthritis,and chagas disease(American trypanosomiasis),Toll-like re-ceptor signaling pathway,apoptosis,colorectal cancer,NF-kappa B signaling pathway,etc.T.wilfordii mainly plays a role in the treat-ment of immune diseases and cancer by regulating inflammatory signaling pathways and cancer signaling pathways.Its action on apopto-sis pathway and drug metabolism enzymes may be the mechanism of its toxicity.