大秦艽汤治疗类风湿关节炎:可能的分子机制和生物研究  

Exploring mechanism of Daqin Gentiana Decoction in treating rheumatoid arthritis based on network pharmacology and molecular docking

作　　者：郑若男 齐笑笑 李建辉 吕雪姣 姜颖[1] ZHENG Ruonan;QI Xiaoxiao;LI Jianhui;LYU Xuejiao;JIANG Ying(School of Basic Medicine,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学基础医学院,哈尔滨150040

出　　处：《哈尔滨商业大学学报（自然科学版）》2023年第6期643-652,675,共11页Journal of Harbin University of Commerce：Natural Sciences Edition

基　　金：黑龙江省博士后科研启动金(LBH-Q21188)。

摘　　要：采用网络药理学和分子对接的方法探究大秦艽汤治疗RA的作用机制.利用中药系统药理学数据库与分析平台(TCMSP)检索大秦艽汤的有效化学成分,通过在线人类孟德尔遗传数据库(OMIM)、基因卡(Gene Cards)、药物银行(Drug Bank)、DisGeNET数据库检索RA的相关靶点.String数据库获得相关蛋白互作的网络构建,导入Cytoscape 3.9.1软件获得药物-活性成分-疾病-作用靶点网络图,对治疗靶点GO功能富集和KEGG通路分析,AutoDockVina分子对接验证.共获得272个药物活性成分和408有效相关靶点,5875个RA疾病靶点,药物与疾病靶点进行匹配,可以获得301个交集靶点蛋白.GO富集分析得出,GO条目共为1462个,细胞组分(cell composition,CC)条目119个,分子功能(molecular function,MF)条目245个,生物过程(biological process,BP)条目1098个;KEGG通路富集分析,主要富集在脂质、胆固醇代谢、癌症和动脉粥样硬化和AGE-RAGE信号通路、HIF-1信号通路、PI3K-AKT信号通路等等;分子对接结果得出,山奈酚与HSP90AA1、MAPK3、STAT3最低结合能较低,其中山奈酚与HSP90AA1最稳定.基于网络药理学与分子对接证明大秦艽汤主要通过STAT3、MAPK3、HSP90AA1、MAPK1等靶基因对炎症因子、缺氧反应、细胞凋亡以及相关功能进行了调节而发挥着治疗类风湿关节炎的作用.To study and explore the relevant targets of Daqin Gentiana Decoction in the treatment of rheumatoid arthritis(RA)through network pharmacology and molecular docking methods,and to explore the mechanism of action in the treatment of RA.The effective chemical components of Daqin Gentiana Decoction were retrieved using the systems pharmacology database and analysis platform of traditional Chinese medicine(TCMSP),and the related targets of RA were retrieved through online human mendelian genetic database(OMIM),gene cards,drug bank,and DisGeNET database.The String database was used to obtain network construction of related protein interactions,and the Cytoscape 3.9.1 software was imported to obtain the drug active ingredient disease action target network diagram.The GO function enrichment and KEGG pathway analysis of treatment targets were performed,and AutoDockVina molecular docking validation was performed.A total of 272 active ingredients and 408 effective related targets were obtained,as well as 5875 RA disease targets.By matching the drug with the disease targets,301 intersecting target proteins were obtained.GO enrichment analysis showed that there were a total of 1462 GO entries,119 cell composition(CC)entries,245 molecular function(MF)entries,and 1098 biological process(BP)entries;KEGG pathway enrichment analysis,mainly in lipid,cholesterol metabolism,cancer and atherosclerosis,AGE-RAGE signaling pathway,HIF-1 signaling pathway,PI3K-AKT signaling pathway,etc;molecular docking results showed that the lowest binding energy of kaempferol with HSP90AA1,MAPK3 and STAT3 was low,and kaempferol with HSP90AA1 was the stablest.Based on network pharmacology and molecular docking,it has been proved that Daqin Gentiana Decoction mainly regulates inflammatory factors,hypoxia response,cell apoptosis,and related functions through target genes such as STAT3,MAPK3,HSP90AA1,and MAPK1,and play a therapeutic role in rheumatoid arthritis.

关 键 词：大秦艽汤 类风湿关节炎 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]