益智防呆方干预阿尔茨海默病的网络药理学探究及实验验证

Network pharmacological exploration and experimental verification of Yizhi Fangdai formula in treatment of Alzheimer's disease

中文关键词: 阿尔茨海默病  益智防呆方  神经炎症  网络药理学  靶点  机制

英文关键词: Alzheimer's disease  Yizhi Fangdai formula  neuroinflammation  network pharmacology  target  mechanism

中文摘要:

      目的 利用网络药理学探究益智防呆方(YZFDF)治疗阿尔茨海默病(AD)的作用靶点和机制,并进行实验验证.方法 联合TCMSP、Drug Bank、Genecards等数据库,筛选YZFDF有效成分及其与AD的交集靶点,筛选YZFDF干预AD核心靶点,进行GO、KEGG富集分析.采用脂多糖诱导BV2小胶质细胞构建AD神经炎症细胞模型,采用RT-qPCR法检测诱导后细胞炎性因子及靶基因的mRNA水平.结果 筛选出YZFDF有效成分133种,与AD交集靶点83个,其中JUN、ALB、CASP3等20个核心靶点.富集分析提示,YZFDF主要通过糖尿病并发症相关AGE-RAGE等多种神经退行性疾病中的通路干预AD.细胞实验结果表明,YZFDF可减少LPS诱导后BV2的激活,减少细胞炎症因子释放,增加神经保护因子表达,减轻神经炎症.结论 YZFDF可能通过β-谷甾醇等有效成分,作用于AKT1、IL-10等核心靶点,参与调控氧化应激、突触传递、细胞凋亡等生物过程,抑制神经炎症,这可能是其治疗阿尔茨海默病的关键机制.

英文摘要:

      Objective To explore the potential action targets and mechanism of Yizhi Fangdai formula(YZFDF)in the treatment of Alzheimer's disease(AD)by means of network pharmacology,and carry out experimental validation.Methods With the aid of databases such as TCMSP,Drug Bank,and Genecards,the effective components of YZFDF and their intersection targets with AD were screened,the core targets of YZFDF intervention in AD were identified,and Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed.An AD neuroin-flammation cell model was established using lipopolysaccharide(LPS)-induced BV2 microglia.Reverse transcription quantita-tive polymerase chain reaction(RT-qPCR)was used to detect mRNA levels of inflammatory cytokines and target genes in the induced cells.Results A total of 133 effective components of YZFDF were screened out,and 83 intersection targets with AD were identified,including 20 core targets such as JUN,ALB,and CASP3.Enrichment analysis suggested that YZFDF mainly intervened in AD through pathways in various neurodegenerative diseases related to diabetic complications,such as AGE-RAGE.The results of cell experiments showed that YZFDF could reduce the activation of BV2 induced by LPS,decrease the release of inflammatory cytokines,increase the expression of neuroprotective factors,and alleviate neuroinflammation.Conclusion YZFDF may act on core targets such as AKT1 and IL-10 through effective components such as β-sitosterol,par-ticipate in regulating biological processes such as oxidative stress,synaptic transmission,and apoptosis,and inhibit neuroin-flammation.This may be the key mechanism for its treatment of Alzheimer's disease.