基于网络药理学探讨荷叶抗非酒精性脂肪肝的作用机制

Mechanism of action of lotus leaf in treatment of nonalcoholic fatty liver disease:A study based on network pharmacology

目的:基于网络药理学探讨荷叶抗非酒精性脂肪肝(NAFLD)的作用机制。方法:利用TCMSP平台和Swiss Target Prediction等数据库搜集荷叶活性成分和作用靶点。通过GeneCard、GenCLiP3数据库获取NAFLD的相关靶点,利用Cytoscape 3.8.2软件构建荷叶成分-疾病-靶点蛋白网络。使用STRING数据库和Cytoscape 3.8.2软件构建蛋白质-蛋白质相互作用(PPI)网络,进行基因本体(GO)功能与京都基因与基因组百科全书(KEGG)通路富集分析。结果:获得荷叶活性成分15种,潜在靶点441个,疾病相关靶点1316个,成分-疾病-靶点161个。PPI网络显示,丝氨酸/苏氨酸蛋白激酶、白细胞介素6、肿瘤抑制基因p53、血管内皮生长因子、肿瘤坏死因子等靶点与荷叶抗NAFLD的关系最密切。GO功能主要有药物的反应、凋亡过程的负调控、胞液、核浆、细胞质、线粒体酶结合、细胞因子活性、转录因子结合等。KEGG通路主要涉及乙型肝炎、癌症的途径、肿瘤坏死因子(TNF)信号通路、Toll样受体信号通路、NOD样受体信号通路、缺氧诱导因子-1信号通路等。结论:荷叶通过调控161个靶点参与TNF信号通路、Toll样受体信号通路、NOD样受体信号通路等作用于NAFLD。

Objective:To investigate the mechanism of action of lotus leaf in the treatment of nonalcoholic fatty liver disease(NAFLD)based on network pharmacology.Methods:TCMSP platform and databases including Swiss Target Prediction were used to obtain the active components and action targets of lotus leaf.GeneCard and GenCLiP3 databases were used to obtain the targets of NAFLD,and Cytoscape 3.8.2 software was used to construct a component-disease-target protein network.STRING database and Cytoscape 3.8.2 software were used to construct a protein-protein interaction(PPI)network,and gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.Results:A total of 15 active components and 441 potential targets were obtained for lotus leaf,as well as 1316 disease targets and 161 component-disease-target intersecting targets.The PPI network showed that the targets such as serine/threonine protein kinase,interleukin-6,tumor suppressor gene p53,vascular endothelial growth factor,and tumor necrosis factor were closely associated with the anti-NAFLD effect of lotus leaf.GO functions mainly included drug response,negative regulation of apoptosis,cytosol,nucleoplasm,cytoplasm,mitochondrial enzyme binding,cytokine activity,and transcription factor binding,and KEGG pathways mainly involved hepatitis B,cancer pathway,tumor necro-sis factor signaling pathway,Toll-like receptor signaling pathway,nucleotide-binding oligomerization domain-like receptor signaling pathway,and hypoxia-inducible factor-1 signaling pathway.Conclusion:Lotus leaf acts on NAFLD by regulating 161 targets and participating in the pathways such as tumor necrosis factor signaling pathway,Toll-like receptor signaling pathway,and nucleotide-binding oligomerization domain-like receptor signaling pathway.