基于网络药理学探讨清热活血方抗类风湿性关节炎的作用机制

Network Pharmacology-Based Pharmacological Mechanism of Qingre Huoxue Formula against Rheumatoid Arthritis

目的:清热活血在治疗类风湿性关节炎(RA)中效果显著,但其成分多样,作用机制不明,通过网络药理学方法探讨清热活血方抗RA的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)筛选药物成分并利用SwissTargetPrediction数据库预测药物靶点,同时通过药物数据库(Drugbank)和在线人类孟德尔遗传数据库(OMIM)收集疾病靶点。将药物靶点与疾病靶点取交集,拓展并拓扑获取关键靶点,利用DAVID数据库对关键靶点进行基因本体论(GO)分类富集分析和京都基因和基因组百科全书(KEGG)通路富集分析,通过Centiscape计算获取hub节点。结果:从清热活血方中筛选出活性成分31个,预测靶点419个,数据库挖掘疾病靶点共430个。将药物靶点与疾病靶点取交集、拓扑分析获得清热活血方治疗类风湿性关节炎的关键靶点113个,GO分析共获得生物过程、分子功能、细胞组分共479个富集结果。KEGG富集表明清热活血方可能通过MAPK、Estrogen、PI3K-AKT、Thyroid hormone、Neurotrophin、HIF-1、ErbB、FoxO、B cell receptor等通路干预RA。拓扑得到CULI、EP300、HSP90AA1、TP53、HSPA8、CDC5L、UBC、RPS27A共8个干预RA的Hub节点。结论:清热活血方可能通过多靶点、多通路进行调控,达到治疗类风湿性关节炎的作用。

Objective:Qingre Huoxue Formula has significant effects in the treatment of rheumatoid arthritis,but its components are diverse and the mechanism of action is unknown.Therefore,the mechanism of Qingre Huoxue Formula′s anti-RA effect was explored through network pharmacology.Methods:The Chinese medicine system pharmacology database and analysis platform(TCMSP)was used to screen drug components and used SwissTargetPrediction database to predict drug targets.Meanwhile,disease targets were collected through Drugbank and online human Mendelian genetic database(OMIM).Intersect drug targets with disease targets,expand and topologically obtain key targets,use the DAVID database to carry out gene ontology(GO)taxonomic enrichment analysis and Kyoto gene and genome encyclopedia(KEGG)pathway enrichment analysis for key targets,and finally obtain hub targets through Centiscape calculation.Results:A total of 31 active ingredients were selected from Qingre Huoxue Formula,419 targets were predicted,and 430 disease targets were mined in the database.The key targets of Qingre Huoxue Formula for the treatment of rheumatoid arthritis were obtained by intersecting drug targets with disease targets and topological analysis.GO analysis obtained a total of 479 enrichment results of biological processes,molecular functions,and cellular components.KEGG enrichment indicated that Qingre Huoxue Formula may interfere with RA through MAPK,Estrogen,PI3K-AKT,Thyroid hormone,Neurotrophin,HIF-1,ErbB,FoxO,B cell receptor and other pathways.A total of 8 Hub nodes interfering with RA were obtained from the topology by CULI,EP300,HSP90AA1,TP53,HSPA8,CDC5L,UBC,and RPS27A.Conclusion:Qingre Huoxue Formula may play an anti-rheumatoid arthritis role by regulating multi-target and multi-pathway.