摘要
Objective:To explore the molecular mechanism of the prescription for the syndrome of cold-damp-ness obstructing the lung in the treatment of corona virus disease 2019(COVID-19).Methods:The medicinals for the treatment of the syndrome of cold-dampness obstructing the lung,such as Cangzhu(Rhizoma Atractylo-dis),Chenpi(Pericarpium Gitri Reticulatae),Houpo(Cortex Magnoliae Officinalis),Huoxiang(Herba Agastachis),Caoguo(Fructus Tsaoko),Mahuang(Herba Ephedrae),Qianghuo(Rhizoma et Radix Notoptery-gi),Shengjiang(Rhizoma Zingiberis Recens),Binlang(Semen Arecae)in the Diagnosis and Treatment Pro-gram of COVID-19(Trial Version 6)were taken as research subjects,and the combination of these nine me-dicinals can be called Hanshi Zufei Fang(寒湿阻肺方,HSZFF).The active components and targets of each single Chinese materia medica was screened and obtained through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database.The target information related to COVID-19 was retrieved through the Gene-Cards disease-related target database.The medicinal prediction targets were mapped to the disease target to ob-tain the intersection targets.The DAVID database was applied to perform gene ontology(GO)enrichment anal-ysis and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis on the targets;GraphPad Prism 5.0 software was applied to plot the biological process(BP)of GO enrichment analysis,cellular component(CC),molecular function(MF)histograms;OmicShare online software was applied to make KEGG advanced bubble chart;Cytoscape software was applied to visualize the interaction with the targets and Chinese materia medica-components-targets results.Results:Totally 56 key active components of 9 Chinese materia medica for cold-dampness obstructing lung syndrome were screened,and 55 targets were obtained.The results of GO and KEGG enrichment analysis showed that the compound prescription mainly regulated the body's immune re-sponse and reduced inflammation by regulating such signaling pathways of inflammatory response and immune regulation as TNF signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,infuenza A signaling pathway,T cell receptor signaling pathway.Conclusion:HSZFF can eliminate infl ammation and inhibit virus by regulating immune inflammatory factors closely related to the occurrence and development of diseases through multi-component and multi-target.
目的:运用网络药理学方法探讨寒湿阻肺证方治疗新型冠状病毒肺炎(简称:新冠肺炎,Corona Virus Disease 2019,COVID-19)的分子机制。方法:以《新型冠状病毒感染的肺炎诊疗方案(试行第六版)》寒湿阻肺证治疗方药苍术、陈皮、厚朴、藿香、草果、麻黄、羌活、生姜、槟榔(HSZFF)为研究对象,通过TCMSP数据库筛选获取各单味药的活性成分及作用靶点;通过GeneCards疾病相关靶点数据库检索COVID-19相关靶点信息。将预测的药物作用靶点映射至疾病靶点上,获得交集靶点。借助DAVID数据库对交集靶点进行GO富集分析和KEGG通路分析,采用GraphPad Prism5.0软件绘制GO富集分析的生物学过程(biological process,BP)、细胞组分(cellular component,CC)、分子功能(molecular function,MF)柱形图;通过OmicShare在线软件制作KEGG高级气泡图;通过Cytoscape软件对作用靶点互作关系及“药物-成分-靶点”结果进行可视化呈现。结果:筛选得到寒湿阻肺证复方9味中药中56个关键活性成分,55个作用靶点。GO和KEGG富集分析结果显示,复方主要通过调控TNF信号通路、HIF-1信号通路、Toll样受体信号通路、甲型流感信号通路、T细胞受体信号通路等炎症反应和免疫调控信号通路,调节机体免疫应答,调控炎症反应。结论:HSZFF通过多成分、多靶标调控与疾病发生发展密切相关的免疫炎症因子,达到消除炎症、抑制病毒的作用。
基金
We thank for the funding support from the National Natural Science Foundation of China(81873285)。