基于网络药理学探讨葶苈大枣泻肺汤治疗新冠肺炎的作用机制

Study on the mechanism of Tingli Dazao Xiefei decoction in the treatment of COVID-19 based on the network pharmacology

为了探讨葶苈大枣泻肺汤治疗新冠肺炎(COVID-19)的作用机制,采用TCMSP数据库筛选葶苈大枣泻肺汤的主要活性成分及靶点,从GeneCards数据库获取COVID-19相关靶点,采用STRING和Cytoscape进行PPI网络构建,利用Metascape进行GO和KEGG富集分析,并通过Autodock进行分子对接。结果筛选得到葶苈大枣泻肺汤27个活性化合物和39个治疗COVID-19潜在作用靶点,主要成分包括槲皮素、山奈酚等,关键靶点涉及TNF,MAPK1/8,CASP3等。KEGG富集通路146条,涉及IL-17,NF-κB、肺结核等。分子对接结果显示核心化合物槲皮素、山奈酚、异鼠李素、β-谷甾醇与ACE2具有较好的亲和性。因此,葶苈大枣泻肺汤可能通过槲皮素、山奈酚、异鼠李素等活性成分调节TNF,CASP3,MAPK等靶点,与ACE2结合,进而调控IL-17,NF-κB等通路,从而抑制细胞因子风暴和炎症损伤,达到多成分、多靶点、多通路防治COVID-19的效果。

To analyze the mechanism of Tingli Dazao Xiefei decoction in the treatment of COVID-19,TCMSP database was used to screen the main active compounds and related targets,GeneCards database was employed to obtain the targets related with COVID-19,STRING and Cytoscape were used to get the PPI network analysis,Metascape database was applied to predict GO enrichment and KEGG pathway annotation,and Autodock was adopted for molecular docking.According to the results,there were 27 active components involved in Tingli Dazao Xiefei decoction and 39 targets aimed to COVID-19,including quercetin,kaempferol,etc.,core targets such as TNF,MAPK1/8,CASP3.There were 146 KEGG pathways,from which IL-17,NF-κB,tuberculosis got the higher P value.The results of molecular docking showed that the core compounds quercetin,kaempferol,isorhamnetin andβ-sitosterol of Tingli Dazao Xiefei decoction had a good affinity with ACE2.This study showed that quercetin,kaempferol,isorhamnetin of Tingli Dazao Xiefei decoction combined with ACE2,may participate in the IL-17 and NF-κB signaling pathway by regulating TNF,CASP3,MAPK,so as to inhibit cytokine storm and inflammatory injury,which could be applied to prevent COVID-19 by multi-component,multi-target and multi-pathway.