基于网络药理学探讨余甘子治疗糖尿病及其并发症的机制

Study of Yuganzi Based on Network Pharmacology Mechanisms for the Treatment of Diabetes and Its Complications

基于网络药理学方法探讨余甘子治疗糖尿病(DM)、糖尿病肾病(DN)、糖尿病足(DF)的作用靶点、信号通路及潜在的分子生物学作用机制。通过中药系统药理学技术平台(TCSMP)、PubChem数据库筛选出余甘子的有效活性成分及作用靶点;利用DisGenet及GeneCards获取与DM、DN、DF相关的靶点基因;将余甘子活性成分的作用靶点与疾病的靶点基因取交集,得到共同的靶点基因。运用Cytoscape 3.9.1软件构建“成分-靶点-疾病”网络图;借助STRING在线数据库构建蛋白互作PPI网络图,使用Cytoscape 3.9.1软件插件ClueGo对共同靶点进行基因本体(GO)分析和信号通路(KEGG)分析,筛选出潜在的信号通路,并分析其作用机制。通过筛选得到余甘子的有效活性成分有7个,余甘子作用于DM、DN、DF的靶点分别为116、76、34个,余甘子可同时治疗3种疾病的共同靶点有32个。GO富集分析结果显示,余甘子-糖尿病及其并发症的交集基因的生物功能主要涉及到凋亡过程的负调控、细胞增殖、细胞迁移、蛋白质磷酸化、磷脂酰肌醇3激酶(PI3K)信号通路的正向调控等生物学过程。KEGG通路富集结果显示,交集基因主要分布在FOXO信号通路及PI3K-AKT信号通路上。余甘子是一种药食同源的热带水果,其营养价值及药用价值均得到广泛的认可,其作用机制呈现多成分、多靶点、多通路的特点,在临床医学中也常作为预防治疗各种疾病的药物使用。本文从药理作用及网络药理学2个方面研究余甘子治疗DM、DN、DF的作用机制,有利于更加深入全面地了解余甘子的药用价值,为其开发和利用提供理论参考。

Based on a network pharmacology approach,we explored the targets,signaling pathways,and potential molecular biological mechanisms of action of Yuganzi in the treatment of diabetes mellitus(DM),diabetic nephropathy(DN),and dia-betic foot disease(DF).The active ingredients and targets of Yuganzi were screened by the TCM Systemic Pharmacology Platform(TCSMP)and PubChem databases;the target genes related to DM,DN,and DF were obtained by using DisGenet and GeneCards;and the intersection of the target genes of the active ingredients of Yuganzi and the target genes of the diseases was taken to obtain the common target genes.Cytoscape 3.9.1 software was used to construct the"component-target-disease"network diagram,the STRING online database was used to build the PPI network diagram of protein interactions,and the ClueGo plug-in of Cytoscape 3.9.1 software was used to analyze the gene ontology and signaling pathway(KEGG)analysis of the identical target genes.KEGG pathway analysis was employed to screen potential signaling pathways,and we analyzed their mechanisms of action.There were seven valid active components of eugenol,116,76,and 34 targets of eugenol acting on DM,DN,and DF,respectively,and 32 common targets of Yuganzi that can treat these three diseases simultaneously.The results of the GO enrichment analysis showed that the biological functions of the genes associated with Yuganzi-diabetes and its complications were mainly involved in the negative regulation of apoptosis,cell proliferation,cell migration,protein phosphorylation,the positive regulation of phosphatidylinositol 3-kinase(PI3K)signaling pathway,and other biological processes.KEGG pathway enrichment analysis revealed that the intersecting genes were mainly involved in the FOXO and the PI3K-AKT signaling pathway.Yuganzi is a tropical and medicinal fruit.Its nutritional and medicinal value is widely recog-nized,and its mechanism of action involves multiple components,targets,and pathways.It is also often used as a preventive treatment for various diseases in medicine.In this paper,we studied the mechanism of action of Yuganzi in the treatment of DM,DN,and DF from the aspects of pharmacology and network pharmacology,which is conducive to a more in-depth and comprehensive understanding of the medicinal value of Yuganzi and provides theoretical references for its development and utilization.