摘要
采用网络药理学、分子对接技术和超滤实验验证,揭示升麻改善阿尔茨海默病(AD)的作用机制。从TCMSP及Swiss Target Prediction数据库中提取升麻的活性成分及对应目标,借助OMIM、DisGenet和GeneCards数据库收集关于升麻改善AD的相关病因靶标信息。采用Cytoscape 3.9.1软件构建“药物-成分-靶点”的可视化网络交集,从而预测升麻改善AD的潜在靶点。将数据导入STRING数据库进行更深入的分析,利用DAVID数据库对预测的目标进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)路径富集分析。使用PyMOL和AutoDockTools 4.2验证关键成分与目标之间的分子对接效果。最终筛选出具有较高生物学价值的候选化合物,并确定它们可能的作用机制。分析结果共得出142个成分靶点,540个AD疾病靶点,PPI网络筛选IL2、EGFR、GAPDH等核心靶点。GO和KEGG富集分析结果显示,升麻改善AD主要涉及糖基化终产物受体(AGE-RAGE)、癌症蛋白聚糖、HIF-1、PD-1信号通路等,其可能通过对蛋白结合、酶结合、细胞增殖分化的调节发挥作用。超滤实验验证了升麻素、升麻素苷、阿魏酸、异阿魏酸和咖啡酸等成分可与AD相关靶点结合。分子对接验证升麻素、阿魏酸、咖啡酸、异阿魏酸、升麻素苷与核心靶点IL2、EGFR、GAPDH等有较为稳定的结合。升麻中升麻素、阿魏酸、咖啡酸、异阿魏酸、升麻素苷等活性成分可抑制炎症,从而对AD有改善作用,为阿尔茨海默病改善机制研究提供了新思路和新方向。
To reveal the potential mechanism of Rhizoma cimicifugae in improving Alzheimer’s disease(AD)by using network pharmacology,molecular docking technology and ultrafiltration experiment verification.The active components and corresponding targets of R.cimicifugae were extracted from TCMSP and SwissTargetPrediction database,and the AD-related etiology-target information was collected from OMIM,DisGenet and GeneCards database.Using Cytoscape 3.9.1 software,we constructed a visual network intersection of“drugs-component-target”to predict potential therapeutic targets for R.cimicifugae in treating AD.The data was then imported into the STRING database for further analysis.The DAVID database was utilized for functional enrichment analysis of the predicted targets using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking efficacy between key components and target compounds was validated through PyMOL and AutoDockTools 4.2 software.This process ultimately identified candidate compounds with high biological value and established their potential mechanisms of action.The study identified 142 component targets and 540 AD-related disease targets,with PPI network screening revealing key targets including IL2,EGFR,and GAPDH.GO and KEGG enrichment analyses indicate that R.cimicifugae improve Alzheimer’s disease primarily involves the glycosylation end-product receptor(AGE-RAGE),cancer-associated proteoglycans,HIF-1,and PD-1 signaling pathways.These mechanisms may function through regulation of protein binding,enzyme interaction,and cell proliferation/differentiation processes.Ultrafiltration experiment verified that cimifugin,cimicifugoside,ferulic acid,isoferulic acid and caffeic acid could bind to AD-related targets.The molecular docking validation showed that cimifugin,cimicifugoside,ferulic acid,isoferulic acid and caffeic acid had stable binding with the core targets IL2,EGFR and GAPDH.The active components of R.cimicifugae,including cimifugin,cimicifugoside,ferulic acid,isoferulic acid and caffeic acid,inhibit inflammation,thereby exerting therapeutic effects on AD.This discovery provides novel insights and directions for studying the pathogenesis of AD.
作者
蒙蕊
刘强
李赛男
MENG Rui;LIU Qiang;LI Sainan(Changchun Normal University Central Laboratory,Changchun 130032,China)
出处
《长春师范大学学报》
2025年第10期64-71,共8页
Journal of Changchun Normal University
基金
吉林省科技发展计划项目(20240602028RC)
长春师范大学研究生创新项目(YJSCX2025034)。
关键词
升麻
阿尔茨海默病
网络药理学
分子对接
超滤实验
Rhizoma cimicifugae
Alzheimer’s disease
network pharmacology
molecular docking
ultrafiltration experiment
