基于网络药理学和分子对接技术探讨苍膝通痹胶囊治疗骨关节炎的作用机制  

Study on Cangxi Tongbi Capsules in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking

作　　者：张正则 马吉智 孙然 孟凯[2] ZHANG Zhengze;MA Jizhi;SUN Ran;MENG Kai(Shandong University of Traditional Chinese Medicine,Jinan 250000,China;Trauma Orthopedics,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250000,China)

机构地区：[1]山东中医药大学,山东济南250000 [2]山东中医药大学附属医院创伤骨科,山东济南250000

出　　处：《西部中医药》2024年第1期70-79,共10页Western Journal of Traditional Chinese Medicine

摘　　要：目的:采用网络药理学方法及分子对接技术探讨苍膝通痹胶囊治疗骨关节炎(osteoarthritis,OA)的分子机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选苍膝通痹胶囊的活性成分及对应靶点;运用Drugbank、人类基因数据库(the human gene database,GeneCards)、药物靶标数据库(therapeutic targetdatabase,TTD)、比较毒理基因组学数据库(comparative toxicogenomics database,CTD)检索OA的已知疾病靶点;使用Venny平台得到苍膝通痹胶囊治疗OA的药效靶点。运用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”网络,运用STRING数据库建立蛋白-蛋白互作网络(protein-protein interactions,PPI),利用CytoHubba工具对所得PPI网络进行拓扑分析筛选出关键靶点。借助DAVID数据库对作用靶点进行基因本体论功能富集分析(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)获取其潜在作用机制,构建苍膝通痹胶囊“通路-靶点”作用网络。从RCSBPDB数据库获取靶点的晶体结构文件,从Pubchem数据库获取活性成分的结构文件,利用Auto vina软件进行分子对接验证。结果:共得到苍膝通痹胶囊活性成分60个、作用靶点140个。OA疾病靶点469个,苍膝通痹胶囊治疗OA的靶点52个。核心成分有槲皮素、β-谷甾醇、豆甾醇、木犀草素等。核心靶点包括IL-1β、IL-6、VEGFA、MAPK、JUN等。通路主要涉及PI3K-Akt、NF-κB、FoxO、雌激素、MAPK通路等。有效成分在与核心靶点对接中具有较强的结合能力。结论:苍膝通痹胶囊通过调控细胞增殖、抑制炎症等多成分、多靶点、多通路治疗OA。Objective:To discuss the molecular mechanism of Cangxi Tongbi capsules in the treatment of osteoarthritis(OA)using network pharmacology and molecular docking.Methods:TCMSP was used to screen the active ingredients and the corresponding targets of the drug;Drugbank,GeneCards,TTD and CTD databases were applied to search the known disease targets of OA;Venny platform was used to obtain the pharmacodynamic targets of treatment of OA by the capsules.Cytoscape 3.7.2 software was used to construct"the drug-ingredient-targets-disease"network,STRING database was adopted to establish the PPI network,CytoHubba tool was utilized to perform topology analysis of the PPI network obtained for the key targets.GO and KEGG enrichment analysis of the targets were performed using David database to obtain the potential mechanism,to construct"pathway-targets"functional network of the capsules.Crystal structure file of the targets were obtained from RCSBPDB database,the structure file of active ingredients were gained from Pubchem database,molecular docking validation was performed using Auto vina software.Results:The study has yielded 60 active ingredients of the medicine and 140 targets of action,involving 469 OA targets,and 52 targets of Cangxi Tongbi capsules in the treatment of OA.Core ingredients contained quercetin,β-sitosterol,stigmasterol,luteolin,etc.Core targets covered IL-1B,IL-6,VEGFA,MAPK,JUN and others.Pathways mainly referred to PI3K-Akt,NF-κB,Foxo,estrogen and MAPK.Active ingredients have strong binding ability in docking to core targets.Conclusion:Cangxi Tongbi capsules could treat OA by regulating cell proliferation and inhibiting inflammation via multi-ingredient,multi-target and multi-pathway.

关 键 词：骨关节炎 网络药理学 分子对接 分子机制 苍膝通痹胶囊 

分 类 号：R274.9[医药卫生—中西医结合]