基于网络药理学探讨“桂枝-附子”温通经脉配伍治疗类风湿关节炎的作用机制

目的:基于网络药理学方法,探讨"桂枝-附子"温通经脉配伍治疗类风湿关节炎(rheumatoid arthritis,RA)可能的作用机制。方法:基于中药系统药理学数据库和分析平台,检索"桂枝""附子"的化学成分和潜在靶点,选择口服生物利用度≥30%和类药性≥0.18作为化学成分筛选条件;在Gene Cards数据库中检索RA疾病靶点;利用Cytoscape 3.6.0软件绘制"桂枝附子配伍-化学成分-靶点-RA"网络;使用STRING 11.0在线软件构建蛋白质-蛋白质相互作用网络,并挖掘核心靶点;采用David Bioinformatics Resources数据库对该配伍活性成分潜在靶点网络中的蛋白进行基因本体(gene ontology,GO)功能富集分析和基于京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)的通路富集分析。结果:GO功能富集分析结果提示,"桂枝-附子"温通经脉配伍主要影响半胱氨酸型内肽酶活性参与凋亡过程、肿瘤坏死因子受体超家族结合等过程。KEGG生物通路富集分析结果提示,该配伍通过肿瘤坏死因子信号通路、凋亡等多条通路影响RA的信号转导和疾病进程。结论:本研究从网络药理角度预测了"桂枝-附子"温通经脉配伍治疗RA可能的信号通路,为后续机制研究奠定了一定的基础。

Exploration on Mechanism of“Cinnamomi Ramulus-Aconite”Wentong Meridian Compatibility in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology

OBJECTIVE:To explore the possible mechanism of"cinnamomi ramulus-aconite"Wentong meridian compatibility in the treatment of rheumatoid arthritis(RA)based on network pharmacology.METHODS:Based on the pharmacological database and analysis platform of traditional Chinese medicine system,the chemical constituents and potential targets of"cinnamomi ramulus"and"aconite"were searched,oral bioavailability≥30%and drug-likeness≥0.18 were selected as the conditions for chemical constituents screening.RA targets were retrieved from Gene Cards database.Cytoscape 3.6.0 software was used to draw the network of"cinnamomi ramulus-aconite compatibilitychemical constituents-targets-RA".STRING 11.0 online software was used to establish the PPI network and mine the core targets.Gene ontology(GO)function enrichment analysis was performed on the proteins in the potential target network of the compatible active ingredient by using David Bioinformatics Resources database,and pathway enrichment was performed based on Kyoto Encyclopedia of Genes and Genomes(KEGG).RESULTS:GO function enrichment analysis suggested that the compatibility mainly affected the activity of cysteine-type endopeptidase to participate into the process of apoptosis,tumor necrosis factor receptor superfamily binding and other process.Enrichment analysis of KEGG biological pathway suggested that the compatibility affected the signal transduction and disease progression of RA through multiple pathways such as TNF signaling pathway and apoptosis.CONCLUSIONS:From the perspective of network pharmacology,this study predicts the possible signal pathway of"cinnamomi ramulus-aconite"Wentong meridian compatibility in the treatment of RA,and lays the certain foundation for the follow-up mechanism research.