基于网络药理学研究六味地黄丸治疗阿尔茨海默病作用机制

    Study on Mechanism of Liuwei Dihuang Pills in Treating Alzheimer’s Disease Based on Network Pharmacology

    • 摘要: 目的 基于网络药理学探讨六味地黄丸治疗阿尔茨海默病(Alzheimer’s disease,AD)的作用机制。方法 从TCMSP数据库筛选六味地黄丸治疗AD的活性成分,并构建药物-靶标网络、蛋白与蛋白相互作用(protein-protein interaction,PPI)网络,运用生物信息学分析方法进行GO分析、KEGG通路富集分析和PPI网络分析。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。结果 分析结果表明,六味地黄丸主要关联AD的β淀粉样蛋白聚集、Tau蛋白的磷酸化、细胞凋亡、氧化应激反应、炎症反应、自噬、胰岛素代谢等;体外实验提示,六味地黄丸参与调控APP介导的β淀粉样蛋白聚集,GSK-3β介导的Tau蛋白磷酸化,GNB1介导的炎症反应,Caspase-3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。结论 六味地黄丸治疗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。

       

      Abstract: OBJECTIVE To explore the mechanism of Liuwei Dihuang pills in the treatment of Alzheimer’s disease(AD) based on network pharmacology. METHODS The active ingredients of Liuwei Dihuang pills in the treatment of AD were screened from the TCMSP database, and the drugs-targets network and protein-protein interaction(PPI) network were constructed. GO analysis, KEGG pathway enrichment analysis and PPI network analysis were performed by bioinformatics analysis methods. The main results of network pharmacology were verified by real-time quantitative PCR. RESULTS The results showed that the targets of Liuwei Dihuang pills were mainly associated with in AD β amyloid protein aggregation, Tau protein phosphorylation, apoptosis, inflammation, oxidative stress response, autophagy and insulin metabolism regulation, etc. In vitro experiments indicated that Liuwei Dihuang pills was involved in the regulation of β amyloid protein aggregation by APP, Tau protein phosphorylation mediated by GSK-3β, inflammation mediated by GNB1, apoptosis mediated by Caspase-3, oxidative stress response mediated by MAOB, autophagy mediated by mTOR, as well as insulin metabolism mediated by INSR. CONCLUSION Liuwei Dihuang pills applied for treating AD has the advantages of multi-components and targets, which can provide references for further research on mechanism.

       

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