基于网络药理学的麻杏石甘汤治疗新型冠状病毒肺炎(COVID-19)作用机制探讨  

Network pharmacological study on mechanism of Maxing Shigan Decoction in treatment of coronavirus disease 2019(COVID-19)

作　　者：王哲义 孙怿泽 曲稔栋 刘碧原[2] 樊竹 田金洲[3] 卢涛 WANG Zhe-yi;SUN Yi-ze;QU Ren-dong;LIU Bi-yuan;FAN Zhu;TIAN Jin-zhou;LU Tao(Beijing University of Chinese Medicine,Beijing 100029,China;School of Life Science,Beijing University of Chinese Medicine,Beijing 100029,China;Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100010,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学生命科学院,北京100029 [3]北京中医药大学附属东直门医院,北京100010

出　　处：《中草药》2020年第8期1996-2003,共8页Chinese Traditional and Herbal Drugs

基　　金：北京市双一流高层次人才科研经费(1000041510053)。

摘　　要：目的通过网络药理学探讨麻杏石甘汤治疗新型冠状病毒肺炎(COVID-19)的作用靶点及信号通路,阐述其可能的作用机制。方法从TCMSP和TCMID数据库搜索麻杏石甘汤4味中药的活性成分及靶点,使用GeneCards及NCBI数据库获取COVID-19靶点;通过STRING数据库构建蛋白质相互作用(PPI)网络。利用Cytoscape 3.7.2软件构建药物-化合物-作用靶点-疾病网络,使用Bioconductor生物信息软件包进行GO功能富集和KEGG通路分析。结果从麻杏石甘汤4味药材中筛选获得127个化合物和相应靶点237个。将麻杏石甘汤主要活性成分调控的靶点与COVID-19的治疗靶点取交集,得到49个关键靶点。GO功能富集分析得到GO条目155个(P<0.01),KEGG通路富集分析筛选得到90条信号通路(P<0.01)。构建药物-化合物-作用靶点-疾病网络,显示槲皮素、山柰酚、柚皮素、木犀草素等活性化合物在整个网络中发挥着关键作用。结论麻杏石甘汤作用于COVID-19的PPI网络中IL-6、TNF、MAPK8、MAPK3、CASP3、TP53、IL-10、CXCL8、MAPK1、CCL2、IL-1β、IL-4、PTGS2等靶点起着关键作用,其中IL-6目前是COVID-19诊疗方案临床重症预警指标。这些靶点共同参与调节糖尿病并发症AGE-RAGE、IL-17和TNF等多条信号通路,发挥抗炎、抗病毒、免疫调节等作用,可能是麻杏石甘汤治疗新冠肺炎的潜在机制。Objective To explore the effect targets and signal pathways of Maxing Shigan(MXSG) Decoction, and elaborate its possible mechanisms in the treatment of corona virus disease 2019(COVID-19). Methods The active ingredients and targets of the four traditional Chinese medicines of MXSG Decoction were searched from the TCMSP and TCMID database, and COVID-19 targets were obtained from the GeneCards and NCBI databases;A protein-protein interaction(PPI) network was constructed through the STRING database. Cytoscape 3.7.2 software was used to create a drug-component-target-disease network. Bioconductor bioinformatics software package was used to perform gene ontology(GO) function enrichment and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis. Results MXSG Decoction contained four herbs, 127 compounds, and 237 corresponding targets. The targets of the main active ingredients of MXSG Decoction were intersected with the therapeutic targets of COVID-19, obtaining 49 key targets. GO function enrichment analysis yielded 155 GO entries(P < 0.01), and KEGG pathway enrichment analysis generated 90 signal pathways(P < 0.01). Construction of a drug-component-target-disease network indicated that nine compounds(e.g. quercetin, kaempferol, naringenin and luteolin) played a key role in the entire network. Conclusion Using the PPI network analysis, we found MXSG Decoction acting on COVID-19 through key molecular targets, such as IL-6, TNF, MAPK8, MAPK3, CASP3, TP53, IL-10, CXCL8, MAPK1, CCL2, IL-1β, IL-4, PTGS2, etc. Among which, IL-6 is currently a clinical early-warning indicator for severe COVID-19 diagnosis and one of the major therapeutic targets. These targets participate cooperatively in the regulation of multiple signaling pathways, such as AGE-RAGE signaling pathway in diabetic complications, IL-17, and TNF signaling pathway, thereby exerting anti-inflammatory, antiviral and immune-regulatory effects.

关 键 词：新型冠状病毒肺炎 麻杏石甘汤 网络药理学 疫毒 炎症 槲皮素 山柰酚 柚皮素 木犀草素 

分 类 号：R285.5[医药卫生—中药学]