基于网络药理学和分子对接预测研究香加皮对类风湿关节炎的治疗作用机制

A study on the therapeutic mechanism of Xiangjiapi on rheumatoid arthritis based on network pharmacology and molecular docking technique

目的:运用网络药理学方法及分子对接技术预测探究香加皮对类风湿关节炎的治疗作用机制。方法:用数据库和文献找出香加皮的有效成分及有效靶点、类风湿关节炎相关靶点、香加皮与类风湿关节炎的交集靶点,采用网络药理学方法构建中药与疾病的关联图、蛋白质-蛋白质相互作用网络图,并进行基因本体论(GO)及京都基因与基因组百科全书(KEGG)分析筛选拓扑学参数排名靠前的成分和靶点,用分子对接来验证对接结合程度。结果:香加皮的有效成分共24种,通过网络药理学筛选出了8个潜在核心成分与9个潜在核心靶点进行分子对接,发现结合能均≤-5 kcal/mol,且大部分结果<-7 kcal/mol;GO主要富集涉及细胞外基质解体、活性氧代谢以及炎症反应的调节等生物过程;主要通路涉及肿瘤坏死因子信号通路、晚期糖基化终末产物-糖基化终末产物受体信号通路、炎症介质对瞬时受体电位通道的调控、白细胞介素-17信号通路等。结论:本研究初步揭示了香加皮对类风湿关节炎具有多成分、多靶点、多途径干预作用机制,可能起到治疗作用,为临床研究提供科学参考。

Objective:A network pharmacological approach and molecular docking technique were used to predictively investigate whether Xiangjiapi(Cortex Periplocae) has a therapeutic mechanism of action in treating rheumatoid arthritis.Methods:The database and literature were used to identify the active ingredients and effective targets of Xiangjiapi,rheumatoid arthritis-related targets,and intersection targets of Xiangjiapi and rheumatoid arthritis,and the network pharmacology method was used to construct the correlation map between TCM and diseases and PPI network map,and GO and KEGG analyses were carried out,and the topranked components and targets in the topological parameter were screened out for molecular docking to validate the docking and binding degree.Results:A total of 24 active ingredients of Xiangjiapi were screened out by network pharmacology,and 8 potential core components were molecularly docked with 9 potential core targets,and it was found that the binding energies were all ≤-5 kcal/mol,and most of them were <-7 kcal/mol.The main GO enrichment involved the extracellular matrix disassembly,reactive oxygen species metabolism,and the regulation of inflammation response.The main pathways involved TNF signaling pathway,AGE-RAGE signaling pathway,regulation of TRP channels by inflammatory mediators,IL-17 signaling pathway and other pathways.Conclusion:This study preliminarily reveals the intervention mechanism of Xiangjiapi in treating rheumatoid arthritis,which has the characteristics of multiple components,multiple targets,and multiple pathways,and may play a therapeutic role.It providing scientific reference for its clinical research.