基于网络药理学和分子对接探讨柴胡桂枝汤治疗类风湿性关节炎的作用机制  

Study on the Mechanism of Action of Bupleurum and Cinnamon Twig Decoction in Treating Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

作　　者：李俊辉 王琳[2] 王芳 LI Jun-hui;WANG Lin;WANG Fang(Luoyang Orthopedic-Traumatological Hospital of Henan Province,Henan Provincial Orthopedic Hospital,Zhengzhou,Henan,China,450016;Henan University of Chinese Medicine,Zhengzhou,Henan,China,450046)

机构地区：[1]河南省洛阳正骨医院,河南省骨科医院,河南郑州450016 [2]河南中医药大学,河南郑州450046

出　　处：《河南中医》2023年第6期823-830,共8页Henan Traditional Chinese Medicine

摘　　要：目的:基于网络药理学及分子对接分析柴胡桂枝汤治疗类风湿性关节炎(rheumatoid arthritis,RA)的作用机制。方法:运用TCMSP对柴胡桂枝汤的有效成分及作用靶标进性筛选,通过相关疾病数据库收集类风湿性关节炎相关靶点,绘制韦恩图得到药物活动成分与疾病相关靶点的共同靶点。借助String数据库和Cytoscape软件构建蛋白质相互作用(protein-protein interaction,PPI)网络,并使用Cytoscape对网络进行拓扑分析,获取核心靶点,通过R语言进行GO富集分析和KEGG通路富集分析,最终将核心基因与主要活性成分进行分子对接验证。结果:共筛选到柴胡桂枝汤中有效成分263个及潜在作用靶点163个,拓扑分析得到MAPK14、HIF1A、AKT1、STAT1、RELA、MAPK1、FOS、STAT3、MAPK3等15个核心作用靶点。KEGG通路富集分析筛选得到柴胡桂枝汤治疗类风湿性关节炎179条通路,主要包含脂质和动脉粥样硬化、PI3K-Akt通路、化学致癌的受体激活、AGE-RAGE信号通路集中抗炎调节免疫。分子对接结果表明,有效成分能分别与核心靶点结合,具有良好的亲和力。结论:柴胡桂枝汤治疗类风湿性关节炎具有多靶点、多成分、多通路的特点,其可能通过槲皮素、山柰酚、汉黄芩素、柚皮素、黄芩素等核心活性成分作用于MAPK14、ESR1、RELA、AKT1、MAPK1、FOS、MAPK3等核心靶点,调节PI3K-Akt信号通路、AGE-RAGE信号通路等调节免疫,减轻炎症反应,缓解类风湿关节疼痛。Objective:To analyze the the mechanism of action of Bupleurum and Cinnamon Twig Decoction in Treating Rheumatoid Arthritis(RA)based on network pharmacology and molecular docking.Methods:TCMSP was used to screen the effective ingredients and targets of action of Bupleurum and Cinnamon Twig Decoction.The related targets of RA were collected through relevant disease databases,and a Venn diagram was drawn to obtain the common targets of drug-active ingredients and disease-related targets.The protein protein interaction(PPI)network was built by using String database and Cytoscape software,and topology analysis of the network was performed by using Cytoscape to obtain core targets.GO enrichment analysis and finally,KEGG pathway enrichment analysis were molecular docking verification between the core genes and the main active components were performed by using R language.Results:A total of 263 active ingredients and 163 potential targets were selected from Bupleurum and Cinnamon Twig Decoction.Topology analysis revealed 15 core targets of action,including MAPK14,HIF1A,AKT1,STAT1,RELA,MAPK1,FOS,STAT3,MAPK3.The enrichment analysis of KEGG pathway screened out 179 pathways of Bupleurum and Cinnamon Twig Decoction in the treatment of RA,mainly including lipid and atherosclerosis,PI3K-Akt pathway,receptor activation of chemical carcinogenesis,AGE-RAGE signal pathway and centralized anti-inflammatory and immune regulation.The molecular docking results indicated that the active ingredients could bind to the core targets separately and had good affinity.Conclusion:Bupleurum and Cinnamon Twig Decoction has the characteristics of multiple targets,components,and pathways in the treatment of RA.It may act on core targets such as MAPK14,ESR1,RELA,AKT1,MAPK1,FOS,and MAPK3 through core active ingredients such as quercetin,kaempferol,wogonin,naringin,and baicalin,regulating the PI3K-Akt and AGE-RAGE signaling pathways to regulate immunity,alleviate inflammation,and alleviate rheumatoid joint pain.

关 键 词：类风湿性关节炎 柴胡桂枝汤 细胞免疫 网络药理学 《伤寒论》 张仲景 

分 类 号：R259.843[医药卫生—中西医结合]