基于网络药理学探讨清瘟解热合剂治疗新型冠状病毒肺炎的作用机制

Mechanism Studies of Qingwen Jiere Mixture on Corona Virus Disease 2019 Based on Network Pharmacology

目的本研究通过网络药理学的方法,探讨清瘟解热合剂治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法运用网络药理学对清瘟解热合剂治疗COVID-19的可能作用靶点和通路进行分析,利用中药系统药理学数据库及分析平台(TCMSP)检索相关化学成分和作用靶点。在OMIM和Genecards数据库中查询与COVID-19相关的靶点。将药物靶点和疾病靶点做韦恩图,得到交集靶点。运用DAVID数据库和KOBAS3.0数据库对靶点进行进行基因功能(GO)富集分析和基因通路(KEGG)富集分析。运用Cytoscape 3.7.2构建成分-靶点-通路网络图。结果网络药理学分析结果表示,本研究共收集到清瘟解热合剂活性成分264个,可作用于510个靶点,关键靶点涉及:白细胞介素(IL-6)、肿瘤坏死因子(TNF)、趋化因子配体2(CCL2)等。GO功能富集分析得到283个条目,其中生物条目(BP)226条,分子功能(MF)31条,细胞组成(CC)26条。KEGG通路富集分析共得到232条通路,包含IL-17信号通路、T细胞受体信号通路、Th17细胞分化、肿瘤坏死因子信号通路等。结论通过网路药理学研究,清瘟解热合剂中的有效成分可能通过影响IL-6、TNF、CCL2等靶点的表达,并调控了IL-17信号通路、T细胞受体信号通路、Th17细胞分化、肿瘤坏死因子信号通路等,发挥治疗COVID-19的作用。

Objective To explore the Underlying mechanisms of Qingwen Jiere Mixture(QJM)for the treatment of corona virus desease 2019(COVID-19)by network pharmacology.Methods Compounds in QJM were screened using TCMSP database and relative researches.Uniprot database was used to search the corresponding genes of targets.Key targets in COVID-19 were retrieved from OMIM and Genecards database.The common potential targets between QJM and COVID-19 were imported into STRING database for PPI network.The Gene oncology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of key targets was also conduct to generat the relative pathways based on DAVID and KOBAS3.0 database respectively.The compound-target-pathway network was established using Cytoscape 3.7.2.Results 264 active compounds and 510 targets were obtained from QJM in this study,and 32 candidates were identified which are the potential targets of QJM on COVID-19 after overlaiding,key targets include interleukin(il-6),tumor necrosis factor(TNF),chemokine ligand 2(CCL2),etc.GO functional enrichment analysis resulted in 283 GO entries,including 226 biological processes(BP)entries and 26 cellular component(CC)entries,and 31 molecular function(MF)entries.KEGG pathway enrichment analysis revealed that there were 232 signaling pathways involving IL-17 signaling pathway,Th17 cell differentiation and TNF signaling pathway.Conclusion In summary,our study corroborated the potential mechanisms of QJM on COVID-19.May be effective in the Qingwen Jiere Mixture composition affects the IL-6,the expression of TNF and CCL2,targets,and regulate the IL-17 signaling pathways,T cell receptor signaling pathways,Th17 cell differentiation,tumor necrosis factor signaling pathways,etc.Our study also provided the research fields to study the mechanisms of QJM on SARS-CoV-2 infection in future.