基于网络药理学的藏药二十五味肺病丸防治新冠病毒肺炎(COVID-19)可行性分析及机制探讨

Feasibility Analysis and Mechanism Discussion of Tibetan Medicine Ershiwuwei Feibing Pills for Prevention and Treatment of Corona Virus Disease(COVID-19)Based on Network Pharmacology

目的采用网络药理学方法探究藏药二十五味肺病丸防治新型冠状病毒肺炎(COVID-19)的可行性分析及机制探讨。方法基于课题组藏药大复方的研究经验,通过文献调研,筛选出二十五味肺病丸专属性、特征性化合物,并通过Chemical book数据库以及TCMSP数据库进行验证,确定二十五味肺病丸有效物质成分。将筛选出的成分通过Swiss Target Prediction数据库进行靶点筛选,进而运用Cytoscape软件构建药物-化合物-靶点(基因)网络进行可视化。运用CTD数据库查询与疾病COVID-19相关的靶点,找出与二十五味肺病丸共有的靶点,将共有基因导入STRING数据库生成蛋白互作网络,并通过DAVID数据库进行KEGG通路富集分析和GO功能富集分析,预测藏药二十五味肺病丸的作用机制。结果经筛选藏药二十五味肺病丸中檀香、悬钩木、山柰、红花、獐牙菜、甘草、藏木香、宽筋藤等19种药材被纳入到研究中。药材-化合物-靶点网络包含了19种药材,38个化合物和相应靶点419个。通过CTD数据库查询到COVID-19疾病相关靶点基因472个,与二十五味肺病丸共有靶点基因77个,分别为ESR1、NOS2、PPARG、PTGS2、PPARA、HMGCR、CYP17A1、NR1H4、TLR9等。通过网络拓扑和蛋白互作网络分析筛选出关键靶点涉及PTGS2、ESR1、AKT1、EGFR等。GO功能富集分析得到339条生物过程条目(BP),45条细胞组成条目(CC)和81条分子功能条目(MF)。KEGG通路富集分析筛选得到102条信号通路,包括小细胞肺癌、非小细胞肺癌、膀胱癌、甲型流感、胰腺癌、T细胞受体信号通路等。结论二十五味肺病丸可能通过作用于PTGS2、ESR1、AKT1、EGFR相关靶点并通过相关肺病通路、炎症通路、免疫通路对COVID-19起到防治作用。

Objective To perform the feasibility analysis and mechanism discussion of the Tibetan medicine Ershiwuwei Feibing Pill for the prevention and treatment of corona virus disease(COVID-19)based on a network pharmacological approach.Methods Based on the research experience of the group on Tibetan medicine compounding,the specific and characteristic compounds of Ershiwuwei Feibing Pill were screened through literature research and verified by Chemical book database and TCMSP database to identify the active substance components of Ershiwuwei Feibing Pill.The screened ingredients were screened again by Swiss Target Prediction database for target screening,and then the drugcompound-target(gene)network was constructed by Cytoscape software for visualization.The CTD database was used to search for targets related to the disease COVID-19 and to identify targets shared with Erxuoyi Pulmonary Pill.The shared genes were imported into the STRING database to generate a protein interaction network,and the KEGG pathway enrichment analysis and GO function enrichment analysis were performed in the DAVID database to predict the mechanism of action of Ershiwuwei Feibing Pill.Results Nineteen Chinese medicinals,including Tanxiang(Lignum Santali Albi),Xuangoumu(Ramulus Rubi),Shannai(Rhizoma Kaempferiae),Honghua(Flos Carthami),Zhangyacai(Swertia bimaculata),Gancao(Radix Glycyrrhizae),Zangmuxiang(Inula racemosa),Kuanjinteng(Tinospora sinensis)and so on were selected for the study.The medicinal material-compound-target network network contains 19 herbs,38 compounds and 419 corresponding targets.The CTD database was queried and 472 COVID-19 disease-related target genes were identified,and 77 target genes were shared with Erwulan Pill,which were ESR1,NOS2,PPARG,PTGS2,PPARA,HMGCR,CYP17 A1,NR1 H4,TLR9,etc.The key targets were screened by network topology and protein interaction network analysis involving PTGS2,ESR1,AKT1,EGFR,etc.GO functional enrichment analysis yielded 339 biological process entries(BP),45 cell composition entries(CC)and 81 molecular function entries(MF).102 signaling pathways were screened by KEGG pathway enrichment analysis,including small cell lung cancer,non-small cell lung cancer,bladder cancer,influenza A,pancreatic cancer,and T-cell receptor signaling pathways.Conclusion Twenty-five Lung Disease Pills may act against COVID-19 by acting on PTGS2,ESR1,AKT1,EGFR-related targets and through related lung disease pathways,inflammatory pathways,and immune pathways.Conclusion Ershiwuwei Feibing Pill may prevent and treat COVID-19 by acting on PTGS2,ESR1,AKT1,and EGFR related targets and through related lung disease pathways,inflammation pathways,and immune pathways.