摘要
目的采用网络药理学和分子对接方法探讨正阳汤治疗新型冠状病毒肺炎的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)搜索正阳汤组方中9味中药的活性成分及作用靶点。利用GeneCards数据库筛选COVID-19相关的靶点,利用R软件将药物靶点与疾病靶点取交集,将交集靶点输入STRING平台获得蛋白互作关系的PPI网络,找寻正阳汤治疗COVID-19的关键靶点并绘制柱状图。利用Cytoscape 3.7.0软件,构建“中药-有效成分-靶点-疾病”关系网络图并进行分析。对筛选出的基因靶点进行GO功能富集分析和KEGG信号通路富集分析。最后利用PyMoL,AuTo Dock软件对正阳汤中核心化合物与新型冠状病毒(SARS-CoV-2)3CL水解酶进行分子对接,预测其作用机制。结果正阳汤中有206个活性成分,116个药物作用靶点;药物与疾病的交集靶点有19个。GO富集得到74条条目,KEGG富集到AGE-RAGE信号通路、细胞凋亡通路、IL-17信号通路、HIF-1信号通路等109条通路。槲皮素、β-谷甾醇、山奈酚、叶黄素、异鼠李素均能与3CLpro结合形成氢键且分子对接结合能较低。结论正阳汤中主要活性成分:槲皮素、β-谷甾醇、山柰酚、叶黄素、异鼠李素等多种活性成分可能通过作用于CASP3、IL-6、MAPK8、EGFR、FOS、CASP8等多种关键靶点调控多条关键信号通路,发挥治疗新冠肺炎的作用。
Objective To investigate the mechanism of Zhengyang Decoction(正阳汤)for treatment of COVID-19 based on network pharmacology and molecular docking.MethodsTraditional Chinese Medicine Systems Pharmacology Data base and Analysis Platform(TCMSP)was used to obtain the active components and targets information of ZYD.The GeneCards data bases were used to obtain COVID-19 targets.The protein-protein interaction network was established by String database to analyze key targets.The herb-compound-target-disease network was established using Cytoscape 3.7.0.Using the R application can get the gene oncology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis of key targets.The molecular docking was performed using PyMoL,and Auto Dock software.ResultsNetwork pharmacology analysis indicated that 206 active compounds and 116 relative targets were selected.A total of 19 targets related to COVID-19 were identified.Finally,the enrichment analysis of GO function was 74 and KEGG to AGE-RAGE signaling pathway,apoptosis pathway,IL-17 signaling pathway,HIF-1 signaling pathway and other 109 pathways.The active ingredients with the lower molecular docking binding energy acting on SARS-CoV-23 CL hydrolase were quercetin,beta-sitosterol,kaempferol,lutein,isorhamnetin.ConclusionThe main compounds of Zhengyang decoction are quercetin,beta-sitosterol and kaempferol,which can regulate multiple signal pathways through key targets such as CASP3,IL-6,MAPK8,EGFR,FOS,CASP8.
作者
王秀芳
原亚利
刘德
姚娓
WANG Xiufang;YUAN Yali;LIU De;YAO Wei(Second Affiliated Hospital of Dalian Medical University,Dalian 116023,Liaoning,China;Dalian Medical University,Dalian 116044,Liaoning,China)
出处
《实用中医内科杂志》
2021年第6期32-37,I0006-I0009,共10页
Journal of Practical Traditional Chinese Internal Medicine
基金
全国中医临床特色技术传承骨干人才培训项目(国中医药教函[2019]36)
辽宁省高等学校基本科研项目(0Q2017032)。
关键词
正阳汤
新型冠状病毒肺炎
网络药理学
分子对接
信号通路
Zhengyang decoction(正阳汤)
Corona Virus Disease 2019(COVID-19)
Network pharmacology
Molecular docking
Signaling pathway
