马鞭草-虎杖抗新型冠状病毒肺纤维化机制的生物信息学分析  

Mechanism of Verbena officinalis-Polygonum cuspidatum in intervention against pulmonary fibrosis due to coronavirus disease 2019:A bioinformatics analysis

作　　者：陈雯雯[1] 张锋[1] 邓建男 CHEN Wenwen;ZHANG Feng;DENG Jiannan(Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430014,Hubei,China)

机构地区：[1]武汉市中医医院,湖北武汉430014

出　　处：《湖南中医杂志》2024年第10期132-138,共7页Hunan Journal of Traditional Chinese Medicine

基　　金：湖北省武汉市医学科研项目(WZ21Z13);湖北省武汉市中医药科研重点项目(WZ22A11)。

摘　　要：目的:利用生物信息学探析马鞭草-虎杖抗新型冠状病毒(COVID-19)肺纤维化(PF)的主要成分和靶点,并探讨其作用机制。方法:在TCMSP、PharmMapper获得活性成分与靶点,通过GeneCards收集疾病基因。采用Cytoscape构建“药物-成分-靶点”相互作用网络,获得关键成分。通过STRING、Metascape构建蛋白质-蛋白质相互作用(PPI)网络筛选关键靶点。对靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,对关键成分与血管内皮生长因子受体(VEGFR)、成纤维细胞生长因子受体(FGFR)和蛋白激酶B1(AKT1)进行分子对接。结果:马鞭草-虎杖抗COVID-19-PF的关键成分为白藜芦醇、毒扁豆次碱、儿茶素、大黄素、艾黄素等。筛选出的核心靶点为细胞肿瘤抗原p53(TP53)、AKT1、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、雌激素受体1(ESR1)、表皮生长因子受体(EGFR)等。GO功能分析显示主要涉及细胞增殖调控、缺氧反应、炎症反应、转录调控等。KEGG通路分析显示主要涉及TNF、白细胞介素-17(IL-17)、磷酯酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)等信号通路。其中与VEGFR对接结合能最低的为艾黄素,与FGFR、AKT1对接结合能最低的均为β-谷甾醇。结论:马鞭草-虎杖通过调控PI3K/AKT、炎症和抗病毒等相关通路,减少细胞外基质的产生、减轻胶原沉积、抑制成纤维细胞的迁移等机制发挥对COVID-19-PF的治疗作用。Objective:To investigate the main components and targets of Verbena officinalis-Polygonum cuspidatum in intervention against pulmonary fibrosis(PF)due to coronavirus disease 2019(COVID-19)based on a bioinformatics analysis,as well as its mechanism of action.Methods:TCMSP and PharmMapper were used to obtain active components and targets,and GeneCards was used to collect disease genes.Cytoscape was used to construct a drug-component-target interaction network and obtain the key components.STRING and Metascape were used to construct a protein-protein interaction network and identify they key targets.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the targets,and molecular docking was performed between the key targets and the mole-cules of vascular endothelial growth factor receptor(VEGFR),fibroblast growth factor receptor(FGFR),and protein kinase B1(AKT1).Results:The key components of Verbena officinalis-Polygonum cuspidatum in intervention against PF due to COVID-19 included resveratrol,physostigmine,catechinic acid,emodin,and artemisetin.The core targets obtained included TP53,AKT1,IL-6,ESR1,and EGFR.The GO functional enrichment analysis showed the involvement of cell proliferation regulation,hypoxia response,inflammatory response,and transcriptional regulation,and the KEGG pathway enrichment analysis showed the involvement of the TNF,IL-17,a nd PI3K/AKT signaling pathways.Artemisetin showed the lowest binding energy to VEGFR,and beta-sitosterol showed the lowest binding energy to FGFR and AKT1.Conclusion:By regulating the PI3K/AKT,inflammation,a nd antiviral signaling pathways,Verbena officinalis-Polygonum cuspidatum can reduce the production of extracellular matrix,alleviate collagen deposition,and inhibit the migration of fibroblasts,thereby exerting a therapeutic effect on PF due to COVID-19.

关 键 词：肺纤维化 COVID-19 马鞭草-虎杖 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]