网络药理学联合分子对接探究大丁草治疗类风湿关节炎的作用机制  

Exploring the action mechanism of Dadingcao in the treatment of rheumatoid arthritis based on network pharmacology combined with molecular docking

作　　者：高长久[1] 张朝立[1] 李文超[1] 王春辉 才玉婷[1] 孟令锴[1] GAO Changjiu

机构地区：[1]牡丹江医学院,黑龙江牡丹江157011

出　　处：《中医临床研究》2024年第10期1-6,共6页Clinical Journal Of Chinese Medicine

基　　金：黑龙江省省属高等学校基本科研业务费科研项目(No.2020-KYYWFMY-0050);牡丹江市应用技术研究与开发计划项目(No.HT2020NS093);黑龙江省卫生健康委科研课题(No.2020-420)。

摘　　要：目的:通过网络药理学联合分子对接技术探究大丁草治疗类风湿关节炎的潜在作用机制。方法:选用化学专业数据库、HERB本草组鉴查找大丁草化学成分,经Swiss ADME数据库筛选出有效成分,应用Swiss Target Prediction预测有效成分的潜在靶点,从Gene Cards、OMIM等数据库查筛类风湿关节炎的靶点,应用Venny 2.1.0数据库获得大丁草与类风湿关节炎交集靶点和韦恩图,采用Cytoscape 3.8.2构建大丁草-有效成分-靶点-类风湿关节炎网络并筛选核心成分,利用Cytoscape插件Biso Genet构建交集靶点蛋白质-蛋白质相互作用网络,经2次筛选获得核心靶点,应用Metascape平台对核心靶点进行富集分析,运用Auto Dock vina将5种核心成分与10个核心靶点进行对接。结果:大丁草治疗类风湿关节炎活性成分有大丁草酚、大丁苷等13种,靶点448个,类风湿关节炎靶点618个,交集靶点101个,核心靶点有雌激素受体1(Estrogen Receptor 1,ESR1)、生长因子受体结合蛋白2(Growth Factor Receptor-Bound Protein 2,Grb2)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)等;通过基因本体论(GO)分析获得调节先天免疫反应等条目,通过京都基因与基因组百科全书(KEGG)分析获得磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)、破骨细胞分化、白细胞介素-17(Interleukin 17,IL-17)等92条通路;核心成分与核心靶点有较好的结合活性。结论:大丁草中大丁草酚、大丁苷等核心成分可能通过ESR1、Grb2、EGFR等靶点,调控PI3K-Akt、MAPK等信号通路来治疗类风湿关节炎。Objective:To explore the potential mechanism of Dadingcao(Herba Leibnitziae Anandriae)in the treatment of rheumatoid arthritis(RA)through network pharmacology combined with molecular docking technology.Methods:The chemical professional database and HERB Materia Medica were used to search out the chemical constituents of Dadingcao,the active constituents were screened out from the SwissADME database,and the potential targets of the active constituents were predicted by SwissTargetPrediction.RA targets were screened from GeneCards,OMIM and other databases.The intersection target and Venn diagram of Dadingcao and RA were obtained by Venny 2.1.0 database.Cytoscape 3.8.2 was used to construct the Dadingcao-active ingredient-targetRA network,and the core components were screened;the Cytoscape plug-in BisoGenet was used to construct the PPI network to obtain the core targets after two screenings.The Metascape platform was used for enrichment analysis of the core targets,the AutoDock vina was used to dock 5 core components with 10 core targets.Results:There were 13 active components of Dadingcao in the treatment of RA,including gerberinol and gerberinside,with 448 targets,618 RA targets,101 intersection targets,and the core targets were ESR1,Grb2,EGFR,etc..GO analysis obtained items such as regulating innate immune responses,and KEGG analysis obtained PI3K-Akt,MAPK,osteoclast differentiation,IL-17 and other 92 pathways,the core components have good binding activity to the core targets.Conclusion:The core components of Dadingcao such as gerberinol and gerberinside may treat RA by regulating PI3K-Akt,MAPK and other signaling pathways through ESR1,Grb 2,EGFR and other targets.

关 键 词：大丁草 类风湿关节炎 网络药理学 分子对接 作用机制 

分 类 号：R274[医药卫生—中医骨伤科学]