摘要
[目的]基于网络药理学研究广佛手成分降血糖的潜在作用靶点。[方法]采用TTD数据库、Drugbank数据库、OMIM数据库和DisGeNET数据库筛选2型糖尿病(T2DM)和高血糖相关基因,借助文献收集广佛手成分,结合Swiss数据库预测其潜在作用靶点。在此基础上,结合STRING数据库筛选关键蛋白,运用Cytoscape 3.7.1软件构建“疾病—活性成分—靶点—通路”关系网络。功能注释方面,进一步通过DAVID 6.8数据库开展基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析。最终,通过AutoDock Vina将广佛手成分活性靶点与关键靶点进行分子对接。[结果]通过网络药理学筛选得到广佛手成分与疾病靶点交集后得到551个相关靶点,构建“成分—靶点—疾病”网络关系图和疾病蛋白质与蛋白质之间的相互作用网络图得到Degree值排名前10的成分和靶点,通过KEGG富集通路筛选出3条与降血糖相关的信号通路。得到广佛手2个主要与降血糖相关的成分(白当归脑和6,6',7,7'-四甲氧基-3,3'双香豆素),3个相关的靶点(HSP90AA1、PIK3CA、PIK3CD)及相关通路(PI3K-Akt信号通路、胰岛素抵抗和HIF-1信号通路),将得到的靶点与通路进行分子对接,得到白当归脑对接HSP90AA1和PIK3CA的结合能分别为-32.6,-34.7 kJ/mol,6',7,7'-四甲氧基-3,3'双香豆素对接PIK3CD和PIK3CA的结合能分别为-35.1,-37.6 kJ/mol。[结论]推测白当归脑和6,6',7,7'-四甲氧基-3,3'双香豆素为广佛手降血糖的主要成分,其可能通过HSP90AA1、PIK3CA、PIK3CD等靶点作用于PI3K-Akt信号通路、胰岛素抵抗和HIF-1信号通路等生物过程来降低血糖。
[Objective]To study the potential targets of hypoglycemic effects of components in Guangdong Finger Citron(GFC)based on network pharmacology.[Methods]Genes associated with type 2 diabetes mellitus(T2DM)and hyperglycemia are screened using the TTD,DrugBank,OMIM,and DisGeNET databases.Active components of GFC are collected from literature,and potential targets are predicted using the Swiss database.Based on this,key proteins are then identified through the STRING database,and a"disease-active-componenttarget-pathway"network was constructed using Cytoscape 3.7.1.Functional annotation is further carried out by performing gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses through the DAVID 6.8 database.Finally,molecular docking of the active components of GFC with key targets was performed using AutoDock Vina.[Results]Through network pharmacology,a total of 551 relevant targets were identified by intersecting the GFC components with disease targets.A"component-target-disease"network is constructed,and the interactions between disease-related proteins are analyzed.The top 10 components and targets are ranked based on their Degree values.KEGG pathway enrichment analysis reveals three signaling pathways related to hypoglycemic effects.Two main GFC components associated with hypoglycemic effects are identified:byakangelicol and 6,6',7,7'-tetramethoxy-3,3'-biscoumarin.Three related targets(HSP90AA1,PIK3CA,and PIK3CD)and associated pathways(PI3K-Akt signaling pathway,insulin resistance,and HIF-1 signaling pathway)are also identified.Molecular docking of the obtained targets with pathways show that byakangelicol has binding energies of-32.6 and-34.7 kJ/mol with HSP90AA1 and PIK3CA,respectively,while 6',7,7'-tetramethoxy-3,3'-biscoumarin has binding energies of-35.1 and-37.6 kJ/mol with PIK3CD and PIK3CA,respectively.[Conclusion]It is speculated that byakangelicol and 6,6',7,7'-tetramethoxy-3,3'-biscoumarin are the main components of GFC for hypoglycemic effects.These components may act by targeting HSP90AA1,PIK3CA,PIK3CD,and other targets to regulate biological processes such as the PI3K-Akt signaling pathway,insulin resistance,and HIF-1 signaling pathway.
作者
马文聪
吴宇箫
钟诚
周爱梅
MA Wencong;WU Yuxiao;ZHONG Cheng;ZHOU Aimei(College of Food Science,South China Agricultural University,Guangzhou,Guangdong 510642,China)
出处
《食品与机械》
北大核心
2025年第5期10-18,共9页
Food and Machinery
基金
广东省自然科学基金(编号:2023A1515011068)
广东省省级科技计划项目(编号:2023B0202010022)。
关键词
网络药理学
分子对接
广佛手
降血糖
T2DM
network pharmacology
molecular docking
Guangdong finger citron
hypoglycemic effect
T2DM
