摘要
目的 运用网络药理学和分子对接技术分析丹蛭降糖胶囊治疗糖尿病肾病(DN)的作用机制.方法 检索TCMSP及相关文献获得丹蛭降糖胶囊组方药物的活性成分及相关靶点,使用UniProt数据库规范靶点基因名;检索GeneCards、OMIM及TTD数据库获得DN相关靶点.利用Venny2.1.0构建韦恩图,获得药物与疾病的交集靶点.采用STRING数据库构建交集靶点蛋白质-蛋白质相互作用网络,采用CytoHubba插件进行拓扑分析,筛选核心靶点.采用Metascape数据库对交集靶点进行GO功能与KEGG通路富集分析.运用AutoDock Vina软件对核心成分与核心靶点进行分子对接.结果 获得丹蛭降糖胶囊活性成分26个,对应靶点267个,核心成分包括槲皮素、木犀草素、山柰酚等.获得853个DN相关靶点,与丹蛭降糖胶囊活性成分靶点的交集靶点109个,核心靶点包括EGFR、TP53、IL6等.GO功能与KEGG通路富集分析显示,丹蛭降糖胶囊可能通过调节糖尿病并发症中AGE-RAGE信号通路、胰岛素抵抗、松弛素信号通路,以及参与酶结合、细胞凋亡、增殖及调控等方面发挥治疗作用.分子对接结果表明,丹蛭降糖胶囊的核心成分与核心靶点之间结构稳定,结合活性良好.其中木犀草素与EGFR结合能最低.结论 丹蛭降糖胶囊可通过多途径发挥治疗DN的作用,能够调控以TNF、STAT3、VGEFA、IL6等关键靶基因为中心的分子网络,调节AGE-RAGE、胰岛素抵抗、松弛素信号通路抑制氧化应激反应及肾组织纤维化.
Abstract
Objective To analyze the molecular mechanism of Danzhi Jiangtang Capsules in the treatment of diabetic nephropathy(DN)by network pharmacology and molecular docking technology.Methods The active components and related targets of Danzhi Jiangtang Capsules were obtained through the TCMSP database and literature search,and UniProt database was used to find the gene name corresponding to the mark;DN-related targets were screened from GeneCards,OMIM,and TTD databases.Venny 2.1.0 was used to construct Venn diagrams to obtain common targets.Then,the common targets were uploaded to the STRING database to build a protein interaction network,and the core targets were mined using CytoHubba.The Metascape database was used for GO functional enrichment analysis and KEGG pathway enrichment analysis for potential targets.Finally,AutoDock Vina software was used to do molecular docking between the core components and the core targets.Results Totally 26 active components of Danzhi Jiangtang Capsules were obtained,corresponding to 267 targets.Its core components included quercetin,luteolin,kaempferol,etc.853 DN related targets and 109 intersecting targets with the active component targets of Danzhi Jiangtang Capsules,with core targets including EGFR,TP53,IL6,etc.GO and KEGG analysis showed that Danzhi Jiangtang Capsules may play a therapeutic role by regulating AGE-RAGE signaling pathway in diabetic complications,insulin resistance,relaxin signaling pathway,and participation in enzyme binding,apoptosis,proliferation,and migration,etc.Molecular docking results showed that the core components of Danzhi Jiangtang Capsules had structurally stable to the core targets,and the binding activity was good.Among them,the binding energy of luteolin and EGFR was the lowest.Conclusion Danzhi Jiangtang Capsules can exert therapeutic effects on DN through multiple pathways,regulating the molecular network centered on key target groups such as TNF,STAT3,VGEFA,and IL6,and regulating AGE-RAGE,insulin resistance and relaxin signaling pathway to inhibit oxidative stress response and renal tissue fibrosis.
国家科技期刊平台
NSTL
维普
万方数据