基于网络药理学探讨牛膝-续断药对在类风湿关节炎中的作用机制

Exploration of mechanism of achyranthes bidentata-dipsacus on rheumatoid arthritis based on network pharmacology

目的:探讨牛膝-续断药对治疗类风湿关节炎(rheumatoid arthritis,RA)的药效物质基础与潜在的作用机制。方法:依托Therapeutic Target Database(TTD)、DrugBank疾病数据库检索出RA已知的靶点,通过中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)找出牛膝-续断的所有化学成分。根据药物口服生物利用度(oral bioavailability,OB)、类药性(drug-likeness,DL)、药物半衰期(drug half-life,HL)等条件筛选成分,列出与其相关的所有潜在靶点。使用韦恩图工具得出疾病靶点和中药成分靶点的共同靶点信息。运用STRING数据库,构建靶蛋白互作(proteinprotein interaction,PPI)网络模型。运用Cytoscape软件插件ClueGO进行KEGG通路注释分析,筛选并得出通路。运用Cytoscape软件构建成分-信号通路-共同靶点网络图。结果:得到RA靶点241个,续断4个成分,牛膝8个成分,药对总计201个靶点。疾病与成分共同靶点为39个。KEGG通路注释分析共得出62条通路。通过网络图预测出药对关键作用成分为槲皮素、山柰酚、汉黄芩素、黄芩素、龙胆根素,关键靶点为TNF,JUN,PTGS2,NFKBIA,IL6,MAPK14,IL1B,关键信号通路为IL-17信号通路、TNF信号通路、Th17细胞分化、NOD样受体信号通路、破骨细胞分化、T细胞受体信号通路、Toll样受体信号通路、NF-κB信号通路、类风湿关节炎。结论:牛膝-续断药对通过槲皮素、山柰酚等成分,作用于TNF,JUN,PTGS2等靶点,IL-17信号通路、TNF信号通路等通路参与其中,在RA中发挥抗炎、免疫保护等治疗作用。

Objective:To investigate the pharmacodynamic basis and potential mechanism of AchyranthesDipsacus in the treatment of rheumatoid arthritis(RA).Methods:According to the Therapeutic Target Database(TTD)and Drug Bank database,the known targets of RA were retrieved.All the chemical components of AchyranthesDipsacus were found by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),according to the oral bioavailability(OB)and drug-likeness(DL),drug half-life(HL)and other conditions to screen the components,listing all potential targets associated with them.The common target information of the disease targets and the targets of the traditional Chinese medicine components was obtained using the Wayne diagram tool.A target protein-protein interaction(PPI)network model was constructed using the STRING database.The KEGG pathway annotation analysis was carried out by using Cytoscape software plug-in ClueGO,and the pathways were screened and obtained.The"component-signal pathway-common target network map"was constructed using Cytoscape software.Results:Two hundred and forty-one targets of RA,four components of Dipsacus,and eight components of Achyranthes bidentata were obtained,and a total of 201 targets of couplet medicines were obtained.There were 39 common targets for the disease and ingredients.A total of 62 pathways were obtained from the KEGG pathway annotation analysis.Through the network diagram,it was predicted that the key components of the drugs were quercetin,kaempferol,baicalin and gentianin,and the key targets were TNF,JUN,PTGS2,NFKBIA,IL6,MAPK14 and IL1 B.The key signaling pathways were IL-17 signaling pathway,TNF signaling pathway,Th17 cell differentiation,NOD-like receptor signaling pathway,osteoclast differentiation,T cell receptor signaling pathway,Toll-like receptor signaling pathway,NF-kappa B signaling pathway and RA.Conclusion:The ingredients such as quercetin and kaempferol contained in Achyranthes bidentata-Dipsacus can act on TNF,JUN,PTGS2 and other targets,involving IL-17 signaling pathway,TNF signaling pathway and other pathways,and exert anti-inflammatory,immunoprotective and other therapeutic effects in RA.