基于网络药理学的生脉散用于COVID-19恢复期治疗的物质基础与作用机制研究

目的:利用网络药理学方法探索“生脉散(SMS)”用于新型冠状病毒肺炎(COVID-19)恢复期治疗的物质基础与作用机制。方法:结合中华人民共和国药典并从TCMSP、在线分析平台(ETCM、TCMID、HIT)以及Chemdb数据库搜索SMS复方中每味中药的归经和成分。药物成分潜在靶标通过PharmMapper、DrugBank、E-TCM和Swiss Target Prediction 4个数据库进行预测。然后,运用String数据库进行SMS药物成分靶标与COVID-19之间靶蛋白相互作用关系的分析,接着利用Cytoscape软件进行网络的构建和分析。最后用DAVID和FunRich数据库对候选靶标进行富集分析。结果:生脉散里的3味中药均归属于肺经,从生脉散复方中共筛选出21个符合选择标准的化学成分,主要包括常见的皂苷类化学成分如人参皂苷Rh4、醇类化学成分如β-谷甾醇,木脂素类化学成分如五味子素,另外还有生物碱类、黄酮类和萜类等化学成分。预测得到中药化学成分相关靶标457个,COVID-19靶标51个。通过String分析发现,化学成分中的70个靶标与COVID-19的29个靶标之间存在着紧密的相互作用;通路富集分析表明,候选靶标富集的通路主要包括癌症相关的多条通路、FoxO信号通路、病毒致癌作用信号通路等。结论:SMS中的有效活性成分可能通过作用于CUL2、NUP62、RAE1等多个靶点进而调节多条信号通路来起到抑制新型冠状病毒肺炎作用,研究结果将为进一步研究提供重要信息依据。

Studies on the Material Basis and Action Mechanism of Shengmai San for the Treatment of COVID-19 in the Recovery Phase Based on Network Pharmacology

Objective:To explore the material basis and mechanism of Shengmai San(SMS)in the treatment of COVID-19 during the recovery period using network pharmacology.Methods:The meridian tropism and composition of each herb in SMS were searched from TCMSP,online analysis platform(ETCM,TCMID,HIT),Chemdb database and chinese pharmacopoeia.Then,PharmMapper database,DrugBank,E-TCM and Swiss Target Prediction platforms were used to predict potential targets of components of SMS.The interaction between proteins of SMS drug components and the key targets of COVID-19 were analyzed by using String database,Cytoscape software was used for network construction and analysis.Finally,DAVID platform and FunRich databases were used for enrichment analysis of candidate targets.Results:It was found that the meridian tropism of the three Chinese herbs in SMS are all lung meridian.A total of 21 chemical components that meet the screen standard were selected from the SMS compound,including common saponin compounds such as ginsenoside Rh4,alcohol compounds such asβ-sitosterol,lignan compounds such as schisandrin,and other chemical components such as alkaloids,flavonoids and terpenes.In addition,457 targets related to the chemical compositions from SMS were predicted,and 51 targets related with COVID-19 disease were obtained.String analysis found that there were close interactions between the 70 targets of the chemical components and the 29 targets of COVID-19;The pathway enrichment analysis showed that the pathways enriched by candidate targets mainly included multiple cancer-related pathways,FoxO signaling pathway,viral carcinogenesis signaling pathway,etc.Conclusion:This paper preliminarily explored the material basis and action mechanism of SMS for the treatment of COVID-19 during the recovery period based on network pharmacology.These results will provide important information for further study.