基于网络药理学及分子对接探讨“桂枝、附子、白术”治疗类风湿关节炎的作用机制

Exploring the mechanism of traditional Chinese medicine"Guizhi-Funzi-Baizhu"for rheumatoid arthritis:based on network pharmacology and molecular docking

目的运用网络药理学的研究方法探究中药“桂枝、附子、白术”治疗类风湿关节炎(RA)的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)检索和筛选桂枝、附子和白术的主要活性成分及其靶点,然后检索GeneCards和DisGeNet等数据库以获取RA的疾病靶点。把药物和疾病的交集靶点导入STRING平台分析蛋白质相互作用并构建蛋白互作网络(PPI)。运用Metascape数据库进行基因本体(GO)功能及京都基因和基因组百科全书(KEGG)通路富集分析,最后用AutoDock对药物主要活性成分和疾病核心靶点进行对接验证。结果“桂枝、附子、白术”调治RA的主要活性成分有20个,包括β-谷甾醇、德尔妥因、3β-白术乙酰基等,作用于白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、IL-1β等36个靶点上,这些靶点主要富集在晚期糖基化终产物及其受体(AGE-RAGE)、TNF、IL-17等多条RA相关通路上。结论中药桂枝、附子、白术治疗RA具有多成分、多靶点、多通路的作用特点,可能主要通过调控炎症因子水平、调节细胞凋亡实现治疗目的。

Objective To explore the mechanism of traditional Chinese medicine(TCM)"Guizhi-Funzi-Baizhu"for rheumatoid arthritis(RA)based on research methods of network pharmacology.Methods The main active ingredients and target of Guizhi,Funzi,Baizhuwere screened in traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),the disease target of RA-related were obtained from Gene Card and DisGeNet databases.Protein-protein interaction(PPI)were performed by intersection targets of drugs and diseases being imported into STRING platform.GO biological process and KEGG pathway enrichment were analyzed using Metascape database,Finally,AutoDock is used to verify the docking of the main compound components of the drug and the core target of the disease.Results Totally 20 main active ingredients were found on regulating RA in"Guizhi-Funzi-Baizhu",of which the ingredientsofβ-sitosterol,deltoin,3β-Atractylodes acetyl,etc,act on 36 target of interleukin 6(IL-6),tumor necrosis factor(TNF),IL-1β,etc.These targets were enriched in advanced glycation end products(AGEs)and their receptors(AGE-RAGE),TNF,IL-17 and other RA related pathways.Conclusion The application of this TCM combination has the characteristics of multi-component,multi-target and multi-pathway,which is capable of achieve the therapeutic by regulating level of inflammatory factors and cell apoptosis.