基于生物信息学探索中药黄精调控铁死亡抗阿尔茨海默病的潜在作用机制  

Exploring the potential mechanism of polygonatum sibiricum in regulating ferroptosis in Alzheimer's disease based on bioinformatics

作　　者：王潇 姚曼 鲁阳光 张瑞 沈雷[1] 王洋[2,3] Wang Xiao;Yao Man;Lu Yangguang;Zhang Rui;Shen Lei;Wang Yang(Basic College,Qiqihar Medical University,Qiqihar 161000;Department of Physiology,Qiqihar Medical University,Qiqihar 161000;Heilongjiang Academy of Chinese Medicine,Heilong jiang 150001)

机构地区：[1]齐齐哈尔医学院基础医学院,黑龙江齐齐哈尔161000 [2]齐齐哈尔医学院生理教研室,黑龙江齐齐哈尔161000 [3]黑龙江省中医药科学院,黑龙江哈尔滨150001

出　　处：《中国现代医药杂志》2024年第4期27-34,共8页Modern Medicine Journal of China

基　　金：齐齐哈尔科学技术局联合引导项目(编号:LSFGG-2023035);齐齐哈尔医学科学院项目(编号:QMSI2021M-11);2023年黑龙江省大学生创新训练项目(编号:S202311232027)。

摘　　要：目的基于生物信息学探索中药黄精调控铁死亡抗阿尔茨海默病(Alzheimer's disease,AD)的潜在物质基础和作用机制。方法利用TCMSP、UniProt数据库筛选黄精有效活性成分并确定作用靶点。通过GeneCards、DrugBank、TTD、GEO数据库获取AD相关疾病靶点。利用Venny图在线工具,筛选黄精治疗AD的潜在靶点。利用Cytoscape 3.9.1软件构建“黄精-有效活性成分-作用靶点”网络图,通过STRING数据库获得蛋白质之间相互作用(PPI)信息。采用Metascape数据库对靶点蛋白进行基因本体(GO)富集和京都基因与基因组百科全书(KEGG)通路富集分析,并进行可视化展示。通过FerrDb数据库检索AD铁死亡过程相关基因,最终得到黄精药物抗AD铁死亡的相关靶点,进一步分析获取核心靶点及其KEGG通路。利用AutoDockTools软件将黄精有效活性成分与核心靶点进行分子虚拟对接以及可视化展示。结果研究筛选黄精有效活性成分18个、黄精治疗AD潜在靶点109个、铁死亡参与AD发病的可能靶点13个、黄精调控铁死亡抗AD核心靶点4个[雄激素受体(AR)、缺氧诱导因子-1(HIF-1)、E3泛素蛋白连接酶mdm2(MDM2)、肿瘤蛋白P53(TP53)]。核心靶点的KEGG通路主要集中在癌症、HIF-1信号通路、IL-17信号通路、化学致癌-受体活化等信号通路。分子对接结果显示,黄精有效活性成分薯蓣皂苷元、黄芩素、芹菜素、异甘草素、3'-甲基黄豆苷元、4',5-二羟基黄酮与核心靶点具有良好的结合能力。结论中药黄精利用薯蓣皂苷元、黄芩素、芹菜素、异甘草素、3'-甲基黄豆苷元、4',5-二羟基黄酮等主要活性成分,通过调控铁死亡相关基因,可有效缓解、改善AD,其机制可能与调控AR、HIF-1、MDM2、TP53蛋白表达及其相关通路有关。Objective To explore the potential active ingredients and mechanism of polygonatum sibiricum(PS)in regulating ferroptosis in Alzheimer's disease(AD)based on bioinformatics.Methods Utilized the TCMSP and UniProt databases to screen active ingredients and determine the effect targets in PS.The targets for AD were retrieved from GeneCards,DrugBank,TTD and GEO databases.Venny diagram was performed to identify potential targets of PS being treated on AD.The network diagram,illustrating the interactions among PS,its active ingredients and targets,was constructed using Cytoscape 3.9.1,with protein-protein interaction(PPI)obtained from the STRING database.The targets were subjected to gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis using the Metascape database,then visualized.Ferroptosis genes were sourced from the FerrDb database and furthermore,the key targets and KEGG pathway were performed.Molecular docking and visualization were carried out using AutoDockTools to elucidate the interaction between active ingredients of PS and key targets.Results Identified 18 active ingredients in PS,109 potential targets involved in treating AD with PS,13 potential targets associated with ferroptosis in AD,and 4 key targets of PS regulating ferroptosis in anti-AD,including androgen receptor(AR),hypoxia-inducible factor-1(HIF-1),E3 ubiquitin-protein ligase mdm2(MDM2),and tumor protein 53(TP53).The KEGG pathway of the key targets mainly focused on cancer,HIF-1 signaling pathway,IL-17 signaling pathway,chemical carcinogenic-receptor activation and other signaling pathways.Molecular docking demonstrated strong binding affinity between PS active ingredients,including Diosgenin,Baicalein,Apigenin,Isoliquiritigenin,3'-Methoxydaidzein,4',5-Dihydroxyflavone,and the key targets.Conclusion Polygonatum sibiricum may alleviate and improve AD by regulating ferroptosis using diosgenin,baicalein,apigenin,isogliquiritin,3'-methyldaidzein,4',5-dihydroxyflavone.The mechanism may involve the regulation of A

关 键 词：黄精 阿尔茨海默病 铁死亡 生物信息学 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]