基于网络药理学和分子对接探讨黑骨藤追风活络胶囊治疗类风湿关节炎的作用机制

Exploring the mechanism of action of Heiguteng Zhuifeng Huoluo capsule in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking

目的基于网络药理学和分子对接探讨黑骨藤追风活络胶囊(HZC)治疗类风湿关节炎(RA)的作用机制。方法通过ETCM数据库和文献查阅获得复方活性成分,运用Swiss Target Prediction平台进行靶点预测。用GeneCards、DisGeNET、OMIM数据库筛选RA相关靶点,绘制韦恩图获取药物和疾病交集靶点。采用STRING平台构建蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape3.9.1软件中centiscape2.2插件筛选潜在关键靶点。用DAVID数据库对关键靶点进行GO功能和KEGG通路富集分析,用Cytoscape3.9.1软件绘制药物-活性成分-靶点-通路网络图。最后选取核心成分与核心靶点进行分子对接。结果共筛选出32个有效成分,药物与疾病交集靶点91个,主要活性成分为槲皮素、盐酸青藤碱和杠柳苷元,核心靶点为肿瘤坏死因子(TNF)、信号转导与转录激活因子3(STAT3)、表皮生长因子受体(EGFR)。作用机制可能与HIF-1信号通路、TNF信号通路、PI3K-Akt信号通路、JAK-STAT信号通路等有关。分子对接显示主要活性成分与关键靶点具有很好的对接活性。结论HZC可通过多靶点、多通路的作用机理治疗RA。

Objective To explore the mechanism of Heiguteng Zhuifeng Huoluo capsule(HZC)in the treatment of rheumatoid arthritis(RA)based on network pharmacology and molecular docking.Methods The active ingredients of the compound were obtained through ETCM database and literature review,and the Swiss Target Prediction platform was utilized for target prediction.The GeneCards,DisGeNET,and OMIM databases were utilized to screen RA-related targets,and Venn diagrams were drawn to obtain drug-disease intersection targets.The protein-protein interaction(PPI)network was constructed using the STRING platform,and the potential key targets were screened using the centiscape2.2 plug-in in Cytoscape3.9.1 software.GO function and KEGG pathway enrichment analysis of key targets were performed using the DAVID database,and the drug-active ingredient-target-pathway network was mapped using Cytoscape3.9.1 software.Finally,the core components were selected for molecular docking with the core targets.Results A total of 32 effective components were screened,and 91 targets of drug and disease intersection were identified.The main active components were Quercetin,Tuduranine Hydrochloride and Periplogenin.The core targets were tumor necrosis factor(TNF),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR).The mechanism of action may be related to HIF-1 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,JAK-STAT signaling pathway and so on.Molecular docking showed that the main active components had good docking activity with the key targets.Conclusion HZC can treat RA through a multi-target and multi-pathway mechanism of action.