基于网络药理学-分子对接探讨益气养阴通络方抗类风湿关节炎的作用机制

Discussion on the mechanism of Yiqi Yangyin Tongluo Recipe in anti-rheumatoid arthritis based on network pharmacology-molecular docking

[目的]采用网络药理学与分子对接探究益气养阴通络方干预类风湿关节炎(RA)的作用机制。[方法]通过中药系统药理学数据库及分析平台(TCMSP)、本草组鉴(HERB)和文献查阅获得复方活性成分与靶点,采用Genecards、在线人类孟德尔遗传数据库(OMIM)等数据库获得疾病靶点,然后采用数据库计算出益气养阴通络复方成分与疾病的交集靶点。对交集靶点施行功能和通路富集分析,选取益气养阴通络方核心药物靶点与关键化合物施行分子对接。[结果]网络药理学共筛选出益气养阴通络方的83种活性成分和779个潜在靶点,RA相关靶点5393个,交集靶点465个,其中交集核心靶点9个(分别为SRC、STAT3、MAPK3、MAPK1、HSP90AA1、PIK3R1、GRB2、AKT1、PIK3CA)。富集得出PI3K-AKT、癌症相关及神经活性配体-受体相互作用等通路,其中PI3K-AKT信号通路可能是复方干预RA的关键通路之一。对接计算表明,益气养阴通络方的11种主要活性成分与关键靶点SRC、STAT3、PIK3R1、AKT1均有较稳定的结合,其中与AKT的结合可能最大。[结论]益气养阴通络方通过多成分-靶点-通路的方式干预RA,PI3K-AKT、癌症相关及神经活性配体-受体相互作用通路均为可能的作用通路。

[Objective]To explore the mechanism of Yiqi Yangyin Tongluo Recipe in intervention of rheumatoid arthritis(RA)by network pharmacology and in vitro experiments.[Methods]In the network pharmacology,first of all,we got the compound active ingredients and targets from TCMSP,HERB and literature,the RA targets from the Genecards and OMIM databases,and the cross-targets of the compound ingredients and RA.Thirdly,the function and pathway enrichment analysis of the intersection target were performed on the Metascape platform,and the molecular docking between the main active ingredients and the core target was performed.[Results]A total of 83 active ingredients,779 potential targets of compound prescriptions,5393 RA-related targets and 465 intersection targets,including 9 intersection core targets(SRC,STAT3,MAPK3,MAPK1,HSP90AA1,PIK3R1,GRB2,AKT1,PIK3CA respectively)were screened by network pharmacology.Enrichment analysis showed the PI3K-AKT,cancer-related and neuroactive ligand-receptor interaction pathways,among which PI3K-AKT signaling pathway may be one of the key pathways.The results of molecular docking showed that the 11 main active components of Yiqi Yangyin Tongluo Recipe had relatively stable binding to the key targets SRC,STAT3,PIK3R1,and AKT1.Among them,the combination with AKT may be the largest one.[Conclusion]Yiqi Yangyin Tongluo Recipe intervenes RA through a multi component-target-tongluo approach.PI3K-AKT,cancer-related and neuroactive ligand-receptor may all be the key interaction pathways.