用网络药理学和分子对接技术探索防风通圣丸治疗COVID-19的机制  

Investigation of the mechanism of Fangfeng Tongsheng Pills in the treatment COVID-19 by network pharmacology and molecular docking

作　　者：高丰 陈莹 戴子琦 郭慧娟 吴倩文 陈红珊 亓金钗 李桐 陈可点 王亚欣 崔鹤蓉 王鹏龙[1] 杜菁 徐冰[1] 雷海民[1] GAO Feng;CHEN Ying;DAI Ziqi;GUO Huijuan;WU Qianwen;CHEN Hongshan;QI Jinchai;LI Tong;CHEN Kedian;WANG Yaxin;CUI Herong;WANG Penglong;DU Jing;XU Bing;LEI Haimin(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Beijing Tongrentang Limited Company,Beijing 100062,China)

机构地区：[1]北京中医药大学,北京102488 [2]北京同仁堂科技发展有限公司,北京100062

出　　处：《西北药学杂志》2022年第2期36-43,共8页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81173519、81603256);新冠肺炎防控应急专项(编号:2020-JYB-YJ-007);北京高精尖学科-系统中药学项目、中央高校基本科研经费项目(编号:2020-JYB-XJSJJ-007);北京市中药基础与新药研究重点实验室项目;中国科学院青年人才培养项目(编号:CACM-2018-QNRC2-B08);北京同仁堂科技发展股份有限公司委托课题项目(编号:G20-01-080)。

摘　　要：目的利用网络药理学和分子对接技术探索防风通圣丸治疗新型冠状病毒肺炎(coronavirus disease 19,COVID-19)的活性成分与作用机制。方法通过中药系统药理学数据库及在线分析平台(traditional Chinese medicine system pharmacology database and online analysis platform,TCMSP)收集防风通圣丸中各味药的主要化学成分及作用靶点;利用GeneCards数据库收集COVID-19的相关靶点,与防风通圣丸化合物靶点取交集筛选出共同靶点,将共同靶点导入Cytoscape软件构建药物-靶点-疾病相互作用网络;将共同靶点导入STRING数据库后在Cytoscape软件中构建蛋白-蛋白相互作用网络图;进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制。运用AutoDock软件对防风通圣丸活性成分与COVID-19关键靶点进行分子对接。结果从防风通圣丸中筛选出224种活性成分共696个作用靶点,与COVID-19重合的靶点有79个,活性化合物有10种(槲皮素、木犀草素、山柰酚、β-谷甾醇和柚皮素等);有效靶点23个(PTGS2、PTGS1、NOS2、F10和DPP4等);经GO分析及KEGG富集分析共得到65条GO富集结果及101条KEGG富集结果,主要涉及炎症反应、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、缺氧诱导因子1(hypoxia inducible factor-1,HIF-1)信号通路、血管内皮生长因子(vascular endothelial growth factors,VEGF)信号通路、Toll样受体(toll-like receptors,TLRs)信号通路、磷脂酰肌醇3激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinase B,PI3K-Akt)信号通路和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路等。结论防风通圣丸中的β-谷甾醇、槲皮素、木犀草素、山柰酚和柚皮素等活性成分可与SARS-CoV-23CL水解酶、ACE2结合,作用于TNF、HIF-1、VEGF、TLRs和MAPK信号通路的TNF、胱天蛋白酶3(caspase-3)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase,MAPK1)、丝裂�Objective To explore the active components and potential mechanism of Fangfeng Tongsheng Pills by using network pharmacology and molecular docking in the treatment of coronavirus disease 19(COVID-19).Methods The main chemical constituents and action targets of various medicines in Fangfeng Tongsheng Pills were collected via traditional Chinese medicine system pharmacology database and online analysis platform(TCMSP).The related targets of COVID-19 were collected by using GeneCards database,and the repeating parts with Fangfeng Tongsheng Pills were taken as the research targets.Cytoscape software was used to create a drug-target-disease network.The common target was imported into STRING database,and the protein-protein interaction network diagram was constructed by Cytoscape software.The GO(gene ontology)function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed by DAVID to predict their mechanism.The core components of Fangfeng Tongsheng Pills were docked with the therapeutic target of COVID-19 by AutoDock software.Results A total of 224 active compounds and 696 active targets were screened from Fangfeng Tongsheng Pills,including 79 targets coincided with COVID-19,and 10 active compounds,i.e.quercetin,luteolin,kaempferol,β-sitosterol,naringenin,etc.,23 effective targets,i.e.PTGS2,PTGS1,NOS2,F10,DPP4,etc.A total of 65 GO function enrichment analysis results and 101 KEGG pathway enrichment results were obtained,including inflammatory response,tumor necrosis factor(TNF)signaling pathway,hypoxia inducible factor-1(HIF-1)signaling pathway,vascular endothelial growth factors(VEGF)signaling pathway,toll-like receptors(TLRs)signaling pathway,phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt)signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion The active components in Fangfeng Tongsheng Pills,such asβ-sitosterol,quercetin,luteolin,kaempferol and naringenin,can combine with SARS-CoV-23CL hydrolase and ACE2,act on the k

关 键 词：防风通圣丸 新型冠状病毒肺炎 网络药理学 分子对接 

分 类 号：R965[医药卫生—药理学]