基于网络药理学和分子对接方法探讨香叶木素治疗高尿酸血症肾病的分子机制  

Molecular mechanism of diosmetin in the treatment of hyperuricemic nephropathy based on network pharmacology and molecular docking

作　　者：雷欢 邓琴 刘子源 张维 徐凌云[1] LEI Huan;DENG Qin;LIU Ziyuan;ZHANG Wei;XU Lingyun(School of Life Science and Technology,Wuhan Polytechnic University,Wuhan 430023,China)

机构地区：[1]武汉轻工大学生命科学与技术学院,武汉430023

出　　处：《山东医药》2022年第14期9-13,24,共6页Shandong Medical Journal

摘　　要：目的基于网络药理学和分子对接的方法,探讨香叶木素治疗高尿酸血症肾病(HN)的分子机制。方法运用中药系统药理学平台(TCMSP)、SwissTargetPrediction数据库、ChEMBL数据库筛选香叶木素的作用靶点基因,借助GeneCards、DisGeNET数据库检索HN疾病靶点基因,运用Venny 2.1在线工具获取香叶木素与HN的共有靶点基因;基于STRING数据库构建共有靶点基因的蛋白质—蛋白质相互作用关系(PPI)网络,通过Cystoscape软件进行可视化分析,拓扑学分析筛选核心靶点基因;借助DAVID数据库对共有靶点基因进行GO功能注释和KEGG通路富集分析。以核心靶点基因编码的蛋白为受体、香叶木素为配体,采用AutoDock Vina 1.1.2软件进行分子对接验证。结果共挖掘出香叶木素潜在作用靶点基因150个、HN相关靶点基因443个,两者共有靶点基因22个。共有靶点基因的PPI网络共包含节点22个、边85条;筛选得到核心靶点基因8个,包括TP53、XDH、ESR1、ABCG2等。富集分析共得到GO功能条目82个,其中生物过程51个(涉及尿酸代谢等)、细胞组成13个(涉及细胞质等)、分子功能18个(涉及跨膜转运蛋白活性等);共富集到35个KEGG信号通路,包括TP53信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路、肿瘤坏死因子(TNF)信号通路、核因子κB(NF-κB)信号通路等。分子对接结果表明,香叶木素与TP53等8个核心靶点基因编码蛋白的结合能均低于-5 kcal/mol,有较强的结合活性。结论香叶木素可能是通过作用于TP53、XDH、ESR1、ABCG2等核心靶点基因,进而调控TP53信号通路、PI3K/Akt信号通路、TNF信号通路、NF-κB信号通路等多条通路发挥对HN的治疗作用。Objective To explore the potential molecular mechanism of diosmetin in the treatment of hyperuricemic nephropathy(HN)based on network pharmacology and molecular docking.Methods Traditional Chinese medicine system pharmacology database and analysis platform(TCMSP),SwissTargetPrediction database and ChEMBL database were used to screen the action target genes of diosmetin,HN-related target genes were searched with the GeneCards database,DisGeNET database,and the common target genes of diosmetin and HN were obtained by Venny 2.1 online mapping tool.The protein-protein interaction(PPI)network of common target genes of diosmetin and HN was constructed based on STRING database,and the visualization analysis and topological analysis were carried out by using Cytoscape 3.7.0 software to obtain the core target genes.GO functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of common targets were analyzed by DAVID database.The protein encoded by the core target genes was taken as the receptor,and diosmetin as the ligand,and the molecular docking verification was carried out by AutoDock Vina 1.1.2.Results Totally 150 potential target genes of diosmetin and 443 HN-related target genes were excavated,and there were 22 common target genes of diosmetin and HN.The PPI network with common target genes included 22 nodes and 85 edges.There were 8 core target genes,including TP53,XDH,ESR1,ABCG2,etc.Eighty-two GO functional items were obtained by enrichment analysis,including 51 biological processes(involving uric acid metabolism),13 cell compositions(involving cytoplasm),and 18 molecular functions(involving transmembrane transporter activity).Thirty-five KEGG signaling pathways were enriched,including TP53 signaling pathway,phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt)signaling pathway,tumor necrosis factor(TNF)signaling pathway,nuclear factor kappa-B(NF-κB)signaling pathway,etc.The results of molecular docking showed that the binding energy between diosmetin and the proteins en

关 键 词：香叶木素 高尿酸血症肾病 网络药理学 分子对接 分子机制 

分 类 号：R692[医药卫生—泌尿科学]