史丽颖, 温泽宇, 宋昱, 于大永. 基于网络药理学与分子对接探究麻黄-桂枝药对治疗类风湿性关节炎机制[J]. 华南师范大学学报(自然科学版), 2023, 55(2): 62-72. doi: 10.6054/j.jscnun.2023021
引用本文: 史丽颖, 温泽宇, 宋昱, 于大永. 基于网络药理学与分子对接探究麻黄-桂枝药对治疗类风湿性关节炎机制[J]. 华南师范大学学报(自然科学版), 2023, 55(2): 62-72. doi: 10.6054/j.jscnun.2023021
SHI Liying, WEN Zeyu, SONG Yu, YU Dayong. Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking[J]. Journal of South China Normal University (Natural Science Edition), 2023, 55(2): 62-72. doi: 10.6054/j.jscnun.2023021
Citation: SHI Liying, WEN Zeyu, SONG Yu, YU Dayong. Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking[J]. Journal of South China Normal University (Natural Science Edition), 2023, 55(2): 62-72. doi: 10.6054/j.jscnun.2023021

基于网络药理学与分子对接探究麻黄-桂枝药对治疗类风湿性关节炎机制

Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

  • 摘要: 通过TCMSP数据库检索麻黄、桂枝中的活性成分以及对应的靶点蛋白,在GeneCards数据库中以“rheumatoid arthritis”为关键词检索类风湿性关节炎(RA)的相关靶点,将收集的2类靶点相互映射取交集后通过STRING平台构建PPI网络,利用Cytoscape软件进行可视化分析;借助David 6.8数据库,对交集靶点进行GO与KEGG富集分析;最后利用Schrodinger软件对核心靶点与关键活性成分进行分子对接验证。2类靶点映射得到交集靶点共134个,PPI分析得到核心靶点为AKT1、IL6、TP53、RELA和CCND1。GO与KEGG富集分析得到关键信号通路为TNF信号通路、Toll样受体信号通路和PI3K-Akt信号通路。分子对接结果显示槲皮素、木犀草素、二氢槲皮素与AKT1、IL6、TP53有较好的结合效果。研究推测麻黄-桂枝药对中的活性成分可能通过抑制炎性介质表达、抑制关节滑膜中树突细胞以及巨噬细胞过量增殖等途径来阻止RA病理发展进程。

     

    Abstract: The active components and corresponding target proteins in Ephedra and Guizhi were retrieved through TCMSP database, and Rheumatoid Arthritis(RA) related targets were retrieved with "rheumatoid arthritis" as the keyword in GeneCards database. After the collected two types of targets were mapped and intersected with each other, PPI network was constructed through STRING platform, and visual analysis was carried out by Cytoscape software. At the same time, the intersection targets were enriched and analyzed by GO and KEGG with the help of David 6.8 database. Finally, the core target and key active components were docking verified by Schrodinger software. Two kinds of targets are mapped, there are 134 intersection targets. PPI analysis shows that the core targets are AKT1, IL6, TP53, RELA and CCND1. Go and KEGG enrichment analysis showed that the key signal pathways were TNF signal pathway, Toll like receptor signal pathway and PI3K-Akt signal pathway. Molecular docking results showed that quercetin, luteolin and dihydroquercetin had good binding effects with AKT1, IL6 and TP53. It is concluded that the active components of Ephedra-Guizhi may play a role in the treatment of rheumatoid arthritis by inhibiting the expression of inflammatory mediators and suppressing the excessive proliferation of dendritic cells and macrophages in joint synovium to prevent pathological progression of RA.

     

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