基于网络药理学的四君子汤治疗阿尔茨海默病作用机制研究

基于网络药理学探讨四君子汤治疗阿尔茨海默病(AD)的作用机制。借助TCMSP数据库及Uniprot数据库筛选出四君子汤有效成分及靶点基因。通过Drugbank、Dis Ge NET和TTD数据库筛选出阿尔茨海默病的靶点基因;成分靶点与疾病靶点映射后使用Cytoscape 3.7.1软件构建药物有效成分-靶点蛋白相互作用网络,使用String数据库绘制靶点蛋白-靶点蛋白相互作用网络;对靶点蛋白利用Metascape数据库进行GO分析和KEGG分析,最后采用荧光实时定量PCR对网络药理学主要分析结果进行验证。分析结果表明,四君子汤主要关联AD的β淀粉样蛋白聚集、细胞凋亡、炎症反应、氧化应激反应、自噬、胰岛素代谢等;体外实验提示,四君子汤参与调控APP介导的β淀粉样蛋白聚集,Caspase-3、Bcl-2、Bax介导的细胞凋亡,MAOB介导的氧化应激反应,mTOR介导的自噬,以及INSR介导的胰岛素代谢等通路。综上四君子汤治疗AD具有多成分、多靶点的特点,可为进一步研究其作用机制提供依据。

Study on mechanism of Sijunzi Decoction in treating Alzheimer's disease based on network pharmacology

To explore the mechanism of Sijunzi Decoction in the treatment of Alzheimer s disease(AD)based on network pharmacology.The effective components and target genes of Sijunzi Decoction were screened by TCMSP da-tabase and Uniprot database.The target genes of Alzheimer s disease were screened by Dragbank,Dis Ge NET and TTD databases.After mapping the component target with the disease target point,Cytoscape 3.7.1 software is used to construct the drug active component-target protein interaction network,and at the same time,the String database is used to draw the target protein-target protein interaction network;The target protein was analyzed by GO and KEGG using Metascape database.Finally,fluorescence real-time quantitative PCR was used to verify the main analysis results of network pharmacology.The results showed that Sijunzi Decoction was mainly associated withβ-amyloid aggregation,apoptosis,inflammation,oxidative stress,autophagy,insulin metabolism etc.of AD.In vitro experiment showed that Sijunzi Decoction was involved in the regulation of APP-mediatedβ-amyloid aggregation,Caspase-3,Bcl-2,and Bax mediated apoptosis,MAOB mediated oxidative stress,mTOR mediated autophagy,and INSR mediated pathways of insulin metabolism.Conclusion demonstrated that Sijunzi Decoction has the characteristics of multi-component and multi-target treatment of AD,and which provided basis for further research on the mechanism of the decoction.