基于网络药理学及分子对接探讨雷公藤治疗白塞病作用机制

Mechanism of Tripterygium wilfordi in treatment of Behcet disease based on network pharmacology and molecular docking

目的 通过网络药理学方法及分子对接探讨雷公藤有效成分治疗白塞病作用机制。方法 应用中药系统药理学分析平台(TCMSP)获取雷公藤活性成分;利用PubChem和SwissTargetPrediction数据库将活性成分转化为基因名;通过Disgenet、GeneCards数据库获取白塞病的疾病靶点;利用Venny 2.1软件绘制雷公藤主要成分基因与白塞病基因的共同靶点韦恩图;应用Cytoscape3.2.1软件构建“雷公藤–主要成分–白塞病”交集基因网络图;利用STRING数据库对其作用靶点构建蛋白相互作用(PPI)网络分析;通过DAVID数据库和微生信软件进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析,筛选出潜在通路并分析其作用机制,并利用分子对接技术验证。结果 从雷公藤中共获得59个生物活性成分,对应的作用靶点561个;白塞病疾病基因984个;通过筛选雷公藤作用于白塞病的共同靶点,得到73个交集基因;其核心靶点为肿瘤坏死因子(TNF)、蛋白激酶B1(Akt1)、基质金属蛋白酶9(MMP9)、信号传导和转录激活蛋白3(STAT3);核心通路为脂质和动脉粥样硬化信号通路、乙型肝炎信号通路、Th17细胞分化信号通路、癌症信号通路、人巨细胞病毒感染信号通路等。分子对接技术显示,去甲黑蔓酮酯与TNF、Akt1靶蛋白的结合能力较强,雷公藤三萜酸A与Akt1靶蛋白的结合能力较强。结论 雷公藤通过多靶点、多途径发挥其整体调节效应而治疗白塞病。

Objective To explore the mechanism of active components of T.wilfordii in treatment of Behcet disease by network pharmacology.Methods The active components of T.wilfordi were obtained by TCMSP.The main components of T.wilfordii were transformed into the gene names by using PubChem and SwissTargetPrediction database.The targets of Behcet disease were obtained from Disgenet and GeneCards database.Venny 2.1 software was used to map the common target of the genes of the main components of T.wilfordi and Behcet disease.Cytoscape3.2.1 software was used to construct the intersection gene network diagram of"T.wilfordi-main component-Behcet disease".The protein interaction network analysis(PPI)of the target was constructed by using STRING database.GO analysis and KEGG pathway enrichment analysis were conducted through DAVID database and Weisheng software to screen out potential pathways and analyze their mechanism of action.The molecular docking was used for validation.Results A total of 59 bioactive components were obtained from T.wilfordi,corresponding to 561 targets.984 genes of Behcet disease.By screening the common targets of T.wifordi on Behcet disease,73 intersection genes were obtained.Its core targets may be TNF,Aktl,MMP9,and STAT3.The core pathways may be lipid and atherosclerosis signaling pathway,hepatitis B signaling pathway,Th17 cell differentiation signaling pathway,cancer signaling pathway,human cytomegalovirus infection signaling pathway,etc.Molecular docking shows that demethylregelin have good binding conformations with the core target of TNF and Aktl,triptotriterpenic acid A have good binding conformations with the core target of Aktl.Conclusion T.wilfordi can exert its global regulatory effect in treatment of Behcet disease through multi target and multi pathway.