基于网络药理学探讨麻黄汤治疗新型冠状病毒肺炎所致发热的分子机制

Molecular mechanism of Mahuang Decoction in treating fever caused by coronavirus disease 2019:a network pharmacology-based analysis

目的通过网络药理学初步探讨麻黄汤治疗新型冠状病毒肺炎所致发热的可能作用机制。方法通过中药系统药理学分析平台获得麻黄汤的有效活性成分及其作用靶点,再在UniProt数据库中利用Perl脚本获取药物靶点对应的人类基因。通过OMIM和GeneCards数据库收集与发热相关的疾病靶点。运用Venny平台获取药物-疾病交集的靶点基因后,通过STRING数据库建立蛋白-蛋白相互作用(PPI)网络。运用R×643.6.1软件对PPI网络中的30个关键基因进行可视化,并对所有交集靶点基因进行功能富集和通路富集分析。结果获得141个麻黄汤有效活性成分及194个药物-疾病交集的靶点基因,筛选出30个关键基因,包括STAT3、AKT1、JUN、MAPK1、IL-6、CXCL2、VEGFA、IL-1B等。交集靶点基因涉及DNA结合转录激活剂活性、RNA聚合酶Ⅱ特异性、细胞因子受体结合、细胞因子活性、泛素样蛋白连接酶结合、核受体活性等170个生物过程,同时主要涉及胞内磷脂酰肌醇激酶-蛋白激酶B信号通路、低氧诱导因子1信号通路、核因子κB信号通路、环磷酸鸟苷-蛋白激酶G信号通路等46个信号通路。结论麻黄汤缓解新型冠状病毒肺炎所致发热的机制是多靶点、多个生物过程、多途径共同参与的,其可能通过抑制炎症反应、减弱病毒活性、保护组织等方面来缓解细胞因子风暴,从而发挥治疗作用。

Objective To preliminarily explore the possible action mechanism of Mahuang Decoction in the treatment of fever caused by coronavirus disease 2019 through network pharmacology.Methods The active ingredients of Mahuang Decoction and their targets were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,the human genes corresponding to drug targets were obtained by using Perl script in the UniProt database.OMIM and GeneCards databases were employed to collect the diseased targets related to fever.Targeted genes were achieved from the intersection of drug-disease genes by using Venny platform,then the protein-protein interaction(PPI)network was constructed by STRING database.R×643.6.1 software was used to visualize the 30 key genes from the PPI network,and function enrichment analysis and pathway enrichment analysis were conducted for all the targeted genes from the intersection.Results Totally 141 active ingredients of Mahuang Decoction and 194 targeted genes from the intersection of drug-disease genes were obtained,and 30 key genes were screened out including STAT3,AKT1,JUN,MAPK1,IL-6,CXCL2,VEGFA and IL-1B.The targeted genes from the intersection mainly involved 170 biological processes,such as DNA-binding transcription activator activity,RNA polymerase Ⅱ specificity,cytokine receptor binding,cytokine activity,ubiquitin-like protein ligase binding,nuclear receptor activity;concomitantly,they mainly involved 46 signaling pathways,including phosphatidylinositol 3-kinase-protein kinase B signaling pathway,hypoxia inducible factor 1 signaling pathway,nuclear factor kappaB signaling pathway,and cyclic guanosine monophosphate-protein kinase G signaling pathway.Conclusion Multi-target,multi-biological process and multi-pathway co-participate in Mahuang Decoction relieving fever caused by coronavirus disease 2019,and it may relieve cytokines storm by inhibiting inflammatory response,attenuating viral activity and protecting tissues,thus exerting a therapeutic effect.