基于网络药理学探讨化湿解毒含片防治新型冠状病毒感染的机制研究

Mechanism of the Huashi Jiedu buccal tablets in the prevention and treatment of COVID-19 based on network pharmacology

目的:通过网络药理学探讨化湿解毒含片防治新型冠状病毒感染的机制,为该方的临床应用提供理论依据。方法:利用中药系统药理学数据库与分析平台(TCMSP)对含片中9种药材的主要有效成分和有关靶标进行检索,并采用Cytoscape软件建立了复方成分-靶点网络;通过Gene Cards数据库获得与新型冠状病毒感染有关的疾病靶标,并将其与药物靶点输入到Venny2.1中,获得药物与疾病的共同靶标,建立韦恩图,利用STRING和Cytoscape软件对关键靶点进行筛选;将得到的核心靶点导入Metascape数据库中进行京都基因与基因组百科全书(KEGG)信号通路富集及基因本体论(GO)富集分析。结果:通过口服生物利用度≥30%和类药性≥0.18进行了筛选;共有187种有效成分,靶点信息共3280个,使用Uni Prot数据库进行基因注释,得到2230个基因符号,构建复方成分-靶点网络;检索出疾病靶点1567个,通过与药物靶点交集后得出公共靶点57个,使用STRING和Cytoscape筛选出关键靶点15个,关键靶点涉及v-akt鼠科胸腺瘤病毒癌基因同源物1(v-akt Murine Thymoma Viral Oncogene Homolog1,AKT1)、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、趋化因子CCL2(C-C Motif Chemokine Ligand 2,CCL2)、白细胞介素-8(Interleukin-8,CXCL8)等;GO富集分析筛选出条目532个,其中生物过程498个、细胞组成14个、分子功能20个;通过KEGG信号的富集分析,获得87条通路,如晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、IL-17信号通路、磷脂酰肌醇-3-激酶(Phosphatidylinositol 3-kinase,PI3K)/Akt信号通路等。结论:研究表明,化湿解毒含片可能通过靶点直接作用或调控多种信号通路等发挥抑制细胞因子风暴及抗病毒作用。因本研究仅局限于数据库信息挖掘,该结论有待进一步实验研究或临床试验加以佐证。

Objective:To explore the mechanism of the Huashi Jiedu buccal tablets(化湿解毒含片)in the prevention and treatment of corona virus disease 2019(COVID-19)by network pharmacology,and to provide a theoretical basis for the clinical application of this formula.Methods:Using the TCMSP database,the main active ingredients and related targets of the nine active ingredients of the tablets were searched,and the compound ingredient-target network was established using Cytoscape software.The disease targets related to COVID-19 were obtained through the GeneCards database,and were imported into Venny2.1 with the drug targets to obtain the common targets of drugs and diseases and establish Venn diagram,and screen the key targets by STRING and Cytoscape software.The obtained core targets were imported into Metascape database for KEGG signal enrichment and GO enrichment analysis.Results:The results showed that 187 active ingredients were screened by oral bioavailability not less than 30%and drug-like properties not less than 0.18,with a total of 3280 targets,and 2230 gene symbols were obtained by gene annotation;UniProt database was used to construct a compound ingredient-target network,1567 disease targets were retrieved,and after intersecting with drug targets,we retrieved 1567 disease targets,57 common targets,and 15 key targets using STRING and Cytoscape,including AKT1,IL-6,TNF,CCL2,CXCL8,etc..A total of 532 entries were screened by GO enrichment analysis,including 498 biological process,14 cell composition and 20 molecular function.87 signaling pathways were obtained by enrichment analysis of KEGG,such as AGE-RAGE,IL-17,PI3K/Akt.Conclusion:This study has shown that the Huashi Jiedu buccal tablets may play a role of inhibiting cytokine storm and antiviral through direct action of targets or regulating various signaling pathways.Since this study is limited to database information mining,this conclusion needs to be further verified by experimental studies or clinical trials.