基于网络药理学探讨甘露消毒汤治疗新型冠状病毒肺炎的作用机制

目的:基于网络药理学的研究方法,探讨甘露消毒汤治疗新型冠状病毒肺炎(COVID-19)的可能机制。方法:采用SPSS Clementine 12.0软件对甘露消毒汤中所有药材的性味归经进行网络关联规则分析;通过中药系统药理学数据库和分析平台、中药系统药理学成分分析平台、中医药综合数据库等数据库,获取甘露消毒汤的活性成分和相对应的作用靶点;通过Gene Cards、人类孟德尔遗传综合数据库,查询物种为"Homo sapiens"对应COVID-19的相关基因,导入软件构建甘露消毒汤-COVID-19-靶点网络;采用STRING数据库,制作活性化合物作用靶点蛋白质-蛋白质相互作用(protein-protein Interaction,PPI)网络,采用R语言中Bioconductor程序包对作用靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,以预测其作用机制。结果:甘露消毒汤中的药材以性微寒,味辛苦,归心、肺、脾、胃经为主;甘露消毒汤中共得到219个药物靶点,COVID-19中共得到259个疾病靶点,最终取交集获得治疗关键靶点25个;GO功能富集得到74条GO条目;KEGG通路富集得到145条信号通路;PPI网络分析发现,EGFR、IL-6、MAPK8、CASP3、FOS、RELA、CASP8、NOS3、PPARG及ICAM1等靶蛋白可能是甘露消毒汤防治COVID-19疾病的潜在关键靶点。结论:甘露消毒汤中的槲皮素、木犀草素、汉黄芩素及山奈酚等成分可能为其治疗COVID-19的有效成分,其机制可能与上述成分作用于多个靶点来发挥抗炎、抗病毒,同时调节免疫等综合作用相关。

Mechanism of Ganlu Xiaodu Decoction on COVID-19 Treatment Based on Network Pharmacology

OBJECTIVE:To probe into the possible mechanism of Ganlu Xiaodu decoction in the treatment of COVID-19 based on network pharmacology.METHODS:SPSS Clementine 12.0 software was used to analyze the network correlation rules of nature flavor and channel tropism of all medicinal materials in Ganlu Xiaodu decoction.The active ingredients and corresponding action targets of Ganlu Xiaodu decoction were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Batman-TCM,TCMID and other databases.GeneCards and OMIM databases were used to search related genes of species Homo sapiens corresponding to COVID-19,and the software was imported to construct Ganlu Xiaodu decoction-COVID-19-target network.The PPI network of active compound targets was made by STRING database,and the gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of active compound targets were performed by using the Bioconductor package in R language to predict the mechanism of action.RESULTS:Ganlu Xiaodu decoction was characterized by mild cold in nature,bitter taste,which was mainly for the heart,lung,spleen and stomach.A total of 219 drug targets were obtained by Ganlu Xiaodu decoction,and 259 disease targets were obtained by COVID-19.Eventually,25 key targets for treatment were obtained by taking the intersection.Totally 74 GO items were obtained from GO functional enrichment.KEGG pathway enrichment resulted in 145 signaling pathways.PPI network analysis showed that EGFR,IL-6,MAPK8,CASP3,FOS,RELA,CASP8,NOS3,PPARG,ICAM1 and other target proteins may be potential key targets for Ganlu Xiaodu decoction to prevent and treat COVID-19 diseases.CONCLUSIONS:Quercetin,luteolin,baicalin,kaempferol and other components in Ganlu Xiaodu decoction may be the effective components in the treatment of COVID-19,and the mechanism may be related to the comprehensive effects of these components by acting on multiple targets,such as anti-inflammatory,antiviral and immune regulation.