基于网络药理学研究麻杏石甘汤治疗冠状病毒感染疾病的作用机制

Mechanism of Maxing Shigan Tang(麻杏石甘汤) in treating COVID⁃19 infection based onnetwork pharmacology

目的 采用网络药理学分析并探讨麻杏石甘汤对重症急性呼吸综合征(SARS)、中东呼吸综合征(MERS)和新型冠状病毒肺炎(COVID-19)可能的共性作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)和TCMID数据库筛选麻杏石甘汤组方中麻黄、苦杏仁、甘草等3味中药的化学成分及相关靶点,通过GeneCrads、DisGeNET和DrugBank数据库筛选SARS、MERS、COVID-19疾病相关靶点,采用Omicshare平台对药物相关靶点和疾病相关靶点进行匹配映射,采用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,采用Cytoscape软件构建“药物-活性成分-关键靶点”交互网络图,通过DAVID和KOBAS数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)信号通路分析。结果 筛选得到麻杏石甘汤防治SARS、MERS和COVID-19的共有靶点48个,信号通路212条。肿瘤蛋白p53(TP53)、血管内皮生长因子(VEGFA)、白细胞介素(IL)-6、胱天蛋白酶3(CASP3)、肿瘤坏死因子(TNF)、有丝分裂原激活蛋白激酶8(MAPK8)、有丝分裂原活化蛋白激酶1(MAPK1)、IL-10等可能是麻杏石甘汤发挥作用的关键靶点,这些靶点主要与免疫调节,炎症,病毒复制,细胞增殖、分化、转化及凋亡等有关,槲皮素、山奈酚、木犀草素、柚皮素、甘草查耳酮α等可能是麻杏石甘汤发挥防治作用的重要共性成分。结论 麻杏石甘汤对SARS、MERS和COVID-19 3种冠状病毒感染疾病存在共性作用机制,主要通过多成分、多把点、多通路达到抑制炎症风暴、调节免疫功能、抗病毒等作用。

Objective To analyze and discuss the possible common mechanism of Maxing Shigan Tang(麻杏石甘汤,MXSGT)on severe acute respiratory syndrome(SARS),middle east respiratory syndrome(MERS)and co⁃rona virus disease 2019(COVID⁃19)based on network pharmacology.Methods The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and traditional Chinese medicine integrated data⁃base(TCMID)were used to screen out the chemical constituents and the related targets of 4 flavors of Chinese ma⁃teria medica(CMM)including Ephedrae herba,Semen Armeniacae Amarum and Glycyrrhizae radix in MXSGT.SARS,MERS and COVID⁃19 disease⁃related targets were screened out through GeneCards,DisGeNET and Drug⁃bank databases,drug⁃related targets and disease⁃related targets were matched and mapped by Omicshare platform,protein⁃protein interaction(PPI)network was constructed by STRING database,and“drug component⁃key target”interaction network was constructed by Cytoscape software,Gene Ontology(GO)and Kyoto Encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out through David and KOBAS databases.Results Forty⁃eight common targets and 212 signal pathways of MXSGT against SARS,MERS and COVID⁃19 were screened out.Tumor protein p53(TP53),vascular endothelial growth factor(VEGFA),interleukin(IL)⁃6,caspase 3(CASP3),tumor necrosis factor(TNF),mitogen activated protein kinase 8(MAPK8),mitogen activated protein kinase 1(MAPK1),IL⁃10 may be the key targets of MXSGT.These targets were mainly related to affecting immune regulation,inflammation,virus replication,cell proliferation,differentiation,transformation and apoptosis.Quercetin,kaempferol,luteolin,naringin and licorice chalcone a may be important common components of MXSGT against the diseases.Conclusion MXSGT has a common action mechanism against SARS,MERS and COVID⁃19,which can inhibit inflammatory storm,regulate immune function,and resist virus through multiple components,multiple tar⁃gets,and multiple pathways.