Based on network pharmacology to explore mechanism of Dabuyuanjian against AD and verification of AMPK/SIRT1 signaling pathway
10.3969/j.issn.1000-484X.2024.08.020
- VernacularTitle:基于网络药理学研究大补元煎防治AD的作用机制及AMPK/SIRT1信号通路验证
- Author:
Mengjie TIAN
1
;
Qinghua LONG
;
Chuhua ZENG
;
Daozhong LIU
;
Ping WANG
;
Lin YUAN
Author Information
1. 湖北民族大学,湿性疾病发生与干预湖北省重点实验室,恩施 445000
- Keywords:
Dabuyuanjian;
Alzheimer's disease;
Network pharmacology;
AMPK/SIRT1 signaling pathway
- From:
Chinese Journal of Immunology
2024;40(8):1692-1700
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of Dabuyuanjian in Against alzheimer's disease(AD)through network phar-macology and molecular docking technology,and to verify the molecular mechanism discovered by animal experiments.Methods:Net-work pharmacology was used to analyze the active ingredients and targets of AD in the treatment of large supplementary yuan decoc-tion.The core components of the drug were verified by molecular docking with the core protein by using AutoDock and PyMOL soft-ware.AD model mice were treated with Dabuyuanjian,and the core pathways which discovered were verified.Results:A total of 80 active ingredients and 107 disease targets were screened out.Dabuyuanjian had 95 targets in the treatment of AD,of which 35 were core targets.GO enrichment found that it mainly involved in programmed cell death process,apoptosis process and signal transduction regulation,etc.KEGG signaling pathway enrichment found that it mainly involved PI3K/Akt signaling pathway,Wnt signaling pathway,AMPK signaling pathway,etc.Morris water maze experiment showed that Dabuyuanjian could reduce the escape latency of AD mice,and increase the number of crossing platform and time's target quadrant.Immunohistochemistry(IHC)showed that Dabuyuanjian could increase the number of positive labeled-NeuN cells in the hippocampal CA3 region of AD mice.Immunofluores-cence(IF)showed that Dabuyuanjian could inhibit the expression levels of(GFAP)and ionized calcium-binding protein 1(IBA1)in the hippocampal CA3 region of AD mice.Western blot experiments showed that Dabuyuanjian could increase the expression levels of phosphorylated adenylate-activated protein kinase α(AMPKα)and silent information regulator 1(SIRT1)in the hippocampus of AD mice.Conclusion:This study explores the mechanism of Dabuyuanjian against AD,and find that Dabuyuanjian can improve cognitive impairment,neuron loss and neuroinflammation via activating AMPK/SIRT1 signaling pathway of AD.
