基于网络药理学探究紫檀芪对阿尔茨海默病的作用及分子机制

Exploring the Effect and Mechanism of Pterostilbene on Alzheimer's Disease Based on Network Pharmacology

目的:基于网络药理学研究紫檀芪抗阿尔茨海默病(Alzheimer’s disease,AD)的潜在靶点和信号通路。方法:利用Swiss Target Prediction数据库筛选获得紫檀芪相关靶点;通过Gene Cards数据库检索获得AD相关靶点;使用Venny 2.1网站获取药物-疾病靶基因的交集;采用STRING数据库获取共同基因的蛋白质间相互作用关系,构建蛋白-蛋白相互作用(protein-protein interaction,PPI)网络;利用Cytoscape 3.7.2软件进行紫檀芪-靶点网络的可视化及分析;使用DAVID数据库对共同基因进行基因本体(gene ontology,GO)富集分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析;使用在线工具进行绘制GO及KEGG通路富集分析图。结果:通过数据库筛选获得紫檀芪相关靶点100个,AD相关靶点14472个,其中有88个为紫檀芪作用于AD的潜在靶点。通过对图中心介值分析发现ESR1、EGFR、MAPT、PTGS2及Bcl-2等为核心靶点。富集分析发现,内分泌抵抗、神经营养信号通路及催乳素信号通路等参与程度非常高。结论:紫檀芪可能通过ESR1、EGFR、MAPT、PTGS2及Bcl-2等核心靶点,调节内分泌抵抗及神经营养信号通路等发挥改善AD的作用。

Objective:Based on network pharmacology,the study aims to explore the potential target and signaling pathway of pterostilbene against Alzheimer's disease(AD).Methods:Swiss Target Prediction database was used to screen the potential targets of pterostilbene;Gene Cards database was used to retrieve the relevant targets of Alzheimer's disease;Venny 2.1 website was employed to obtain the intersection of drug-disease target genes;STRING database was used to construct the protein-protein interaction(PPI)network of common genes;Cytoscape 3.7.2 software was utilized for visualization and analysis of the pterostilbene-target network;DAVID database was employed for gene ontology(GO)enrichment analysis and kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment analysis of common genes;Online tools were used to draw GO and KEGG pathway enrichment analysis diagrams.Results:By database screening,1o0 potential targets of pterostilbene and 14472 Alzheimer's disease-related targets were obtained,among which 88 were identified as potential targets of pterostilbene in Alzheimer's disease.Base on the analysis of Betweenness,ESR1,EGFR,MAPT,PTGS2 and Bcl-2 were core targets.Enrichment analysis showed that endocrine resistance,neurotrophin signaling pathway and prolactin signaling pathway were highly involved.Conclusion:Pterostilbene may regulate endocrine resistance and neurotrophic signaling pathways through core targets such as ESRl,EGFR,MAPT,PTGS2 and Bcl-2 to exert its protective effect against Alzheimer's disease.