基于网络药理学的金藤清痹颗粒治疗类风湿关节炎的作用机制研究  

Mechanism of Jinteng Qingbi Granules in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology

作　　者：翟弋焱 陈美琳 时锐 黄佳奇 张景媛 张繁芹 黄志鸿 谭影影 金政森 高艺菲 陶晓宇 刘鹏芸 吴嘉瑞[1] 雷威[2] ZHAI Yiyan;CHEN Meilin;SHI Rui;HUANG Jiaqi;ZHANG Jingyuan;ZHANG Fanqin;HUANG Zhihong;TAN Yingying;JIN Zhengsen;GAO Yifei;TAO Xiaoyu;LIU Pengyun;WU Jiarui;LEI Wei(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China;Dept.of Traditional Chinese Medicine,Linyi People’s Hospital,Shandong Linyi 276003,China)

机构地区：[1]北京中医药大学中药学院,北京100029 [2]临沂市人民医院中医科,山东临沂276003

出　　处：《中国医院用药评价与分析》2023年第4期385-392,共8页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金项目(No.82074284);国家中医药传承创新团队子项目(No.ZYYCXTD-C-202005-10);北京中医药大学与鲁南厚普制药有限公司联合项目(No.BUCM-2022-JS-FW-034)。

摘　　要：目的:探讨金藤清痹颗粒治疗类风湿关节炎的活性成分及可能的作用机制。方法:通过中药系统药理学数据库与分析平台、DisGeNET及GeneCards等数据库获取金藤清痹颗粒中的化学成分和类风湿关节炎相关靶点。将二者交集靶点导入STRING数据库进行分析,接着使用Cytoscape软件绘制蛋白质-蛋白质相互作用(PPI)网络图、金藤清痹颗粒成分靶点网络图及药物-成分-靶点-通路网络图等。通过R软件对关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。使用AutoDockTools软件对金藤清痹颗粒中的活性成分与其对应的关键靶点进行分子对接验证。结果:筛选得到金藤清痹颗粒中153个化合物,399个化合物相关靶点,131个交集靶点。根据网络拓扑学参数筛选得到关键靶点,分别为蛋白激酶B1(Akt1)、胱天蛋白酶3(CASP3)、表皮生长因子受体(EGFR)、白细胞介素6(IL-6)、肉瘤基因(SRC)、雌激素受体1(ESR1)、缺氧诱导因子1(HIF1)和氨基末端蛋白激酶(JUN)。对PPI网络分析得到151条KEGG通路和2567条GO功能条目;GO条目中包括2294条生物过程相关条目,119条细胞成分和154条分子功能相关条目。分子对接结果表明,槲皮素、木犀草素、β-谷甾醇、3,8-二羟基喹啉和芍药苷等化合物与Akt1、CASP3、EGFR、IL-6、SRC、ESR1、HIF1和JUN等有较好的结合活性。结论:金藤清痹颗粒治疗类风湿关节炎是基于多成分、多靶点的作用机制,本研究为下一步的相关实验验证提供了理论基础。OBJECTIVE:To probe into the active ingredients and possible mechanism of Jinteng Qingbi granules in the treatment of rheumatoid arthritis.METHODS:The chemical ingredients and rheumatoid arthritis-related targets in Jinteng Qingbi granules were obtained through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),DisGeNET,GeneCards and other databases.Intersection targets of the two were imported into the STRING database for analysis,and the results were imported into Cytoscape software to draw the protein interaction(PPI)network map,the ingredients target network map of Jinteng Qingbi granules,and the drug-ingredient-target-pathway network map.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on key targets by R software.Active ingredients in Jinteng Qingbi granules and the corresponding key targets were verified by molecular docking using AutoDockTools software.RESULTS:There were 153 compounds,399 compound-related targets and 131 intersection targets in Jinteng Qingbi granules.Key targets such as protein kinase B1(Akt1),cystatin protease 3(CASP3),epidermal growth factor receptor(EGFR),interleukin 6(IL-6),sarcoma gene(SRC),estrogen receptor 1(ESR1),hypoxia-inducible factor 1(HIF1),and amino-terminal protein kinase(JUN)were screened according to network topology parameters.PPI network analysis yielded 151 KEGG pathways and 2567 GO functional entries.Totally 2294 items related to biological process,119 items related to cellular component and 154 items related to molecular function were included in the GO items.Molecular docking results showed that quercetin,luteolin,beta-sitosterol,3,8-dihydroxyquinoline,paeoniflorin and other compounds had good binding activity to Akt1,CASP3,EGFR,IL-6,SRC,ESR1,HIF1 and JUN.CONCLUSIONS:Jinteng Qingbi granules in the treatment of rheumatoid arthritis is based on the multi-component and multi-target mechanism of action.This study provides a theoretical basis for the next

关 键 词：金藤清痹颗粒 类风湿关节炎 网络药理学 分子对接 机制 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]