基于细胞因子的人参败毒散治疗新型冠状病毒肺炎(COVID-19)的网络药理学研究

Network pharmacology for treatment of COVID-19 with Renshen Baidu Powder based on cytokines

目的从细胞因子角度,探究人参败毒散多成分、多靶点、多途径抗新型冠状病毒肺炎(COVID-19)的作用机制。方法应用中药系统药理分析平台(TCMSP)收集人参败毒散中活性化合物,结合药物靶点数据库收集细胞因子风暴相关靶点,利用Cytoscape构建“药材-化合物-疾病靶点”网络。通过String和DAVID数据库对靶点的互作网络、GO功能和KEGG通路进行分析。结果人参败毒散“药材-活性化合物-疾病靶点”网络包括10种药材,211个活性成分和151个疾病靶点。互作网络发现人参败毒散抑制细胞因子风暴治疗COVID-19的靶点可能包含STAT3、MAPK1、NFκB1、PIK3CA、MAPK3、TNF、CXCR4、VEGFA、IL-6、IL-2等。GO功能分析发现上述靶点在生物功能方面涉及趋化性、类固醇代谢过程等;在分子功能方面涉及血红素结合、铁离子结合、氧结合等;在细胞组成方面涉及细胞表面、细胞膜等。KEGG通路富集发现上述靶点参与查加斯病通路、HIF-1信号通路、肿瘤坏死因子信号通路等的调控。结论人参败毒散可能通过调节趋化性细胞因子,增加血氧饱和度,抑制STAT、MAPK、NFκB、PIK3K、IL-6等炎症相关信号通路,实现多成分-多靶点-多途径抑制细胞因子风暴形成的抗COVID-19作用。

Objective To investigate the multi compound-target-pathway mechanism of Renshen Baidu Powder(RSBDS)in the treatment of COVID-19 from cytokine perspective.Methods The active compounds of RSBDS were collected by TCMSP and the cytokine storm related targets were collected by the drug target database.The interaction network of RSBDS on single drug-active compounds-targets was established by Cytoscape.The interaction network,GO function and KEGG pathway of the targets were analyzed by String and DAVID databases.Results The interaction network of RSBDS on single drug-active compounds-targets included 10 kinds of medicinal materials,211 active compounds and 151 disease targets.Interaction network showed that the targets related to the inhibition to cytokine storm of RSBDS on COVID-19 might include STAT3,MAPK1,NFκB1,PIK3CA,MAPK3,TNF,CXCR4,VEGFA,IL-6,IL-2,etc.GO function showed that above targets in biological function involved chemotaxis and steroid metabolism;Molecular function entries involved heme binding,iron ion binding and oxygen binding;Cell composition entries involved cell surface and cell membrane.KEGG pathway showed that above targets participated in the regulation of Chagas disease,HIF-1 signaling pathway,TNF signaling pathway,etc.Conclusion The multi compound-target-pathways effect of RSBDS on COVID-19 was realized by inhibiting cytokine storm,which through regulating chemotaxis,increasing blood oxygen saturation,inhibiting STAT,MAPK,NFκB,PIK3K and IL-6 signal pathways.