基于网络药理学及实验验证分析人参益智健脑方治疗阿尔兹海默病作用机制
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R285

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浙江省中医药科技计划项目(2023ZL097)


Analysis of Mechanism of Renshen Yizhi Jiannao Prescription in Treating Alzheimer's Disease Based on Network Pharmacology and Experimental Validation
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    摘要:

    目的:分析人参益智健脑方治疗阿尔兹海默病的作用机制。方法:通过TCMSP平台检索人参益智 健脑方的有效成分,并通过Uniprot数据库校正靶点。通过Genecard数据库检索阿尔兹海默病的基因靶点,并 剔除重复基因。将药物靶点与疾病靶点取交集得到人参益智健脑方治疗阿尔兹海默病的潜在靶点。利用 STRING数据库对关键靶点进行蛋白相互作用(PPI) 网络分析。利用R语言进行GO和KEGG通路富集分析, 利用Cytoscape软件构建有效化合物-作用靶点网络。检测不同浓度的人参益智健脑方提取液对BV-2小胶质细 胞存活率的影响。采用Western blot检测BV-2细胞p-p38、p38、p-p65、p65蛋白表达。结果:筛选得到人参益 智健脑方治疗阿尔兹海默病的潜在有效成分共47个,作用靶点360个,阿尔茨海默病靶点14 407个,取交集得 到潜在作用靶点303个。其中槲皮素、山奈酚、间羟基苯甲酸、人参皂甙等可能是关键成分,MAPK1、TP53、 JUN、TNF等可能是关键靶点。GO功能分析提示细胞炎症、氧化应激、神经元凋亡、DNA信号转录等可能是人 参益智健脑方治疗阿尔兹海默病的生物学途径。KEGG通路富集分析共获得172条通路,主要包括脂质和动脉粥 样硬化、糖尿病并发症中的AGE-RACE、IL-17、TNF等信号通路。体外实验表明,人参益智健脑方可以抑制 脂多糖(LPS) 激活的BV-2胶质细胞中p-p38、p-p65蛋白的表达。结论:人参益智健脑方治疗阿尔茨海默病具有 多成分、多靶点、多信号通路的特点,其作用机制可能与抑制MAPK和NF-κB信号通路、减轻神经细胞炎症相关。

    Abstract:

    Abstract:Objective:To analyze the mechanism of Renshen Yizhi Jiannao Prescription in treating Alzheimer's disease(AD). Methods:The active components of Renshen Yizhi Jiannao Prescription were retrieved from the TCMSP platform, and their targets were corrected using the Uniprot database. Gene targets for AD were retrieved from the Genecard database,and duplicate genes were removed. The intersection of drug targets and disease targets was taken to obtain potential targets for Renshen Yizhi Jiannao Prescription in treating AD. The STRING database was used for protein-protein interaction(PPI)network analysis of key targets. GO and KEGG pathway enrichment analyses were performed using R language,and the effective compound-target network was constructed using Cytoscape software. The effect of different concentrations of Renshen Yizhi Jiannao Prescription extract on the survival rate of BV-2 glial cells was detected. Western blot was used to detect the expression of p-p38,p38,p-p65,and p65 proteins in BV-2 cells. Results: A total of 47 potential active components of Renshen Yizhi Jiannao Prescription were identified, acting on 360 targets. For AD, 14 407 targets were identified, with 303 potential therapeutic targets. Quercetin, kaempferol, m-hydroxybenzoic acid,and ginseng oside were identified as potential key components,while MAPK1,TP53,JUN, and TNF were identified as potential key targets. GO functional analysis suggested that cellular inflammation,oxidative stress, neuronal apoptosis, and DNA signal transcription might be the biological pathways through which Renshen Yizhi Jiannao Prescription exerts its effects on AD. KEGG pathway enrichment analysis identified 172 pathways,mainly including lipid and atherosclerosis, as well as AGE-RAGE, IL-17, and TNF signaling pathways in diabetic complications. In vitro experiments showed that Renshen Yizhi Jiannao Prescription could inhibit the expression of p-p38 and p-p65 proteins in LPS-activated BV-2 glial cells. Conclusion: Renshen Yizhi Jiannao Prescription has the characteristics of multiple components,multiple targets,and multiple signaling pathways in treating AD. Its mechanism of action can be related to the inhibition of MAPK and NF-κB signaling pathways and the reduction of neuroinflammation.

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沈浩,朱旭贞.基于网络药理学及实验验证分析人参益智健脑方治疗阿尔兹海默病作用机制[J].新中医,2025,57(19):194-202

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  • 在线发布日期: 2025-10-20
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