神经药理学报 ›› 2023, Vol. 13 ›› Issue (5): 1-.DOI: 10.3969/j.issn.2095-1396.2023.05.001

• 研究论文 •    下一篇

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

张晓然,刘思远,杨浩然,郭轩桐,范乐豪,李金达,金戈,卢方晋,朱琳   

  1. 1. 沈阳医学院基础医学院,沈阳,110034,中国 

    2. 沈阳医学院中医药学院,沈阳,110034,中国 

    3. 沈阳医学院药学院,沈阳,110034,中国

  • 出版日期:2023-10-26 发布日期:2024-05-09
  • 通讯作者: 朱琳,博士研究生,讲师; 研究方向: 主要从事神经药理学相关研究; E-mail: zhulindedream@163.com
  • 作者简介:张晓然,医学影像学本科在读; 研究方向: 主要从事神经药理学相关研究; E-mail: 202220546@qq.com
  • 基金资助:
    辽宁省博士科研启动基金计划项目(No.2021-BS-283); 沈阳医学院大学生科研项目(No.20239093)

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

ZHANG Xiao-ran, LIU Si-yuan, YANG Hao-ran, GUO Xuan-tong, FAN Le-hao, LI Jin-da, ZHU Lin   

  1. Basic Medical College, Shenyang Medical College, Shenyang, 110034, China

  • Online:2023-10-26 Published:2024-05-09
  • Contact: 朱琳,博士研究生,讲师; 研究方向: 主要从事神经药理学相关研究; E-mail: zhulindedream@163.com
  • About author:张晓然,医学影像学本科在读; 研究方向: 主要从事神经药理学相关研究; E-mail: 202220546@qq.com

摘要:

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Venny2.1 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 gene and genome encyclopedia, 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14 472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BCL2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BCL2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。

关键词: 网络药理学, 紫檀芪, 阿尔茨海默病, 靶点, 信号通路

Abstract:

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; Venny2.1 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 gene and genome encyclopedia (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, 100 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 BCL2 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 ESR1, EGFR, MAPT, PTGS2 and BCL2 to exert its protective effect against Alzheimer’s disease.

Key words: network pharmacology, pterostilbene, Alzheimer’s disease, target, signaling pathway