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目的探寻金叶败毒颗粒治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的药理作用机制。方法通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中药分子机制的生物信息学分析工具(Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)检索筛选金叶败毒颗粒中金银花、蒲公英、鱼腥草、大青叶的化学成分和作用靶点。查询OMIM(Online Mendelian Inheritance in Man)、GeneCards数据库获得疾病相关靶点基因,进而运用Cytoscape软件构建药物活性分子-靶点基因作用网络,通过R语言包clusterProfiler进行基因本体(gene ontology,GO)功能注释和基于京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,预测金叶败毒颗粒对COVID-19的作用机制。结果共筛选获得药物活性分子31个。靶点基因110个,主要包含PTGS2、AR、ESR1、PPARG、PRSS1、NOS2、NR3C2等核心靶点。富集分析得到GO条目2 138项(P <0. 05),KEGG信号通路134条(P <0. 05),主要富集的通路有AGE-RAGE信号通路、动脉粥样硬化、TNF-α信号通路、甲型流感等。结论金叶败毒颗粒的活性化合物能作用于TNF信号等核心炎症通路,从而对COVID-19起到抗氧化损伤、抗炎作用。
Abstract：Objective To explore the pharmacological mechanism of Jinyebaidu Particles in the treatment of coronavirus disease 2019(COVID-19). Methods Through searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) to select the chemical constituents and action targets of Lonicerae Japonicae Flos,Houttuyniae Herba,Isatidis Folium,Taraxacum mongolicum Hand.-Mazz in Jinyebaidu Particles. The disease-related target genes were obtained by consulting Online Mendelian Inheritance in Man(OMIM) and GeneCards database,and then the drug-active molecules-target gene action network was constructed using Cytoscape software. Gene ontology(GO) functional annotation and enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were conducted by the R package cluster Profiler to predict the mechanism of action of Jinyebaidu Particles on COVID-19. Results A total of 31 active molecules and 110 target genes were screened,mainly including PTGS2,AR,ESR1,PPARG,PRSS1,NOS2,NR3 C2 and other core targets. Enrichment analysis revealed 2 138 GO items(P < 0. 05)and 134 KEGG signaling pathways(P < 0. 05). The main enrichment pathways included AGE-RAGE signaling pathway,atherosclerosis,TNF-α signaling pathway,Influenza A pathway. Conclusion The active compounds of Jinyebaidu Particles can act on core inflammatory pathways such as TNF signaling,thus exerting antioxidant damage and anti-inflammatory effects on COVID-19.
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基本信息:
DOI：10.16389/j.cnki.cn42-1737/n.2020.06.003
中图分类号:R285
引用信息:
[1]袁发浒,刘丽,巴瑞琪等.基于网络药理学的“金叶败毒颗粒”防治COVID-19作用机制探索[J].江汉大学学报(自然科学版),2020,48(06):23-32.DOI:10.16389/j.cnki.cn42-1737/n.2020.06.003.
基金信息:
国家自然科学基金资助项目(81674060)