基于网络药理学和分子对接探讨红花治疗类风湿性关节炎作用机制

Study on the Mechanism of Honghua against Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学和分子对接技术探究红花治疗类风湿性关节炎的作用机制。方法：通过中药系统药理学分析平台检索红花的活性成分和作用靶点，与GeneCards数据库中抗类风湿关节炎靶点相映射，筛选出红花抗类风湿关节炎作用的潜在作用靶点；利用String数据库和Cytoscape软件构建蛋白互作网络及药物–靶点–作用通路网络，获得抗类风湿性关节炎的关键靶点；运用DAVID数据库进行GO及KEGG富集分析；使用AutoDockVina程序对主要活性成分和关键靶点进行分子对接。通过网络药理学分析得到红花治疗类风湿性关节炎的活性成分22个和靶点51个，关键靶点是RELA和JUN。其中红花的3个主要活性成分：槲皮素、木犀草素、山奈酚，主要通过调控炎症反应、细胞因子的分泌调节、TNF信号通路、T细胞受体等信号通路发挥治疗类风湿性关节炎的作用；分子对接结果显示红花的主要活性成分与关键靶点均有很好的结合作用。结论：本研究通过网络药理学发现红花治疗类风湿性关节炎是多成分、多靶点、多通路的复杂过程，为进一步探究其作用机制奠定了基础。

Abstract: Objective: To explore the mechanism of Honghua against rheumatoid arthritis based on network pharmacology and molecular docking technology. Methods: The active components and targets of Honghua were searched through Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and mapped with the anti-rheumatoid arthritis targets from GeneCards database to screen the potential targets of Honghua in treatment of rheumatoid arthritis. The protein-protein interaction network and drugs-targets-pathways network were constructed using String database and Cytoscape software, and the key anti-rheumatoid arthritis targets were obtained. DAVID database was used for GO and KEGG enrichment analysis. The key targets were docked with major active ingredients using Auto Dock Vina program. 22 active components and 51 targets of Honghua in treatment of rheumatoid arthritis were obtained through network pharmacology analysis, and RELA and JUN were the key targets. Three main active components of Honghua: Quercetin, Luteolin, Kaempferol played an important role in the treatment of rheumatoid arthritis through the regulation of inflammatory response, cytokine secretion regulation, TNF signaling pathway, T cell receptor and other signaling pathways. The molecular docking results showed that the main active components of Honghua had good binding affinity on the key targets. Conclusion: Through network pharmacology, this study found that Honghua treatment of rheumatoid arthritis was a complex process with multiple components, multiple targets and multiple pathways, which lays a foundation for further exploring its mechanism of action.