Research on the Pharmacodynamic Material Basis and Mechanism of Action of the Chinese Medicine Compound GAPT Intestinal Absorption Solution in Treating Alzheimer's Disease
10.16466/j.issn1005-5509.2024.12.001
- VernacularTitle:中药复方金思维肠吸收液治疗阿尔茨海默病的药效物质基础及作用机制研究
- Author:
Lan MA
1
;
Jing SHI
;
Fuyao LI
Author Information
1. 北京中医药大学东直门医院 北京 100700;浙江中医药大学附属温州市中医院
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
GAPT;
PI3K/AKT/GSK-3β signaling pathway;
human neuroblastoma cells;
HPLC-MS;
intestinal absorption solution;
network pharmacology;
dementia
- From:
Journal of Zhejiang Chinese Medical University
2024;48(12):1467-1481
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To determine the main components of Chinese medicine compound GAPT intestinal absorption solution and conduct network pharmacology analysis,and explore its mechanism of action in treating Alzheimer's disease(AD) and conduct experimental verification.[Methods]The common components of GAPT intestinal absorption solution and GAPT stock solution were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS),the common components were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database,the drug targets were queried by SWISS database,and the AD targets were queried by DrugBank,OMIM,GeneCards,DisGeNET and TTD databases. Venn analysis of drug targets and disease targets yielded the key targets of GAPT for the treatment of AD. Protein-protein interaction(PPI) analysis was performed using the STRING database and PPI network was plotted using Cytoscape 3.7.2 software. Key targets were imported into the Metascape platform for gene ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Correlation network relationships were visualized using Cytoscape 3.7.2 software. Finally,according to the results of network pharmacology analysis,the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) signaling pathway was selected for cell experimental verification.[Results]A total of 73 eligible active ingredients were screened,among which Corydaline,Sinensetin,Skullcapflavone Ⅱ,Liquiritigenin,Palmatine were key components in the treatment of AD with GAPT intestinal absorption solution. PPI network analysis suggested that AKT1 was the core targets for preventing and treating AD. KEGG analysied suggests that the prevention and treatment of AD with GAPT intestinal absorption solution may involve PI3K/AKT signaling pathway,calcium signaling pathway,cyclic adenosine monophosphate(cAMP) signaling pathway,etc. The results of cell experiments showed that the proportion of phosphorylated-AKT(p-AKT) protein was significantly reduced in model group compared to normal group(P<0.01);the expression level of phosphorylated-glycogen synthase kinse-3β/glycogen synthase kinse-3β(p-GSK-3β/GSK-3β) protein in model group was significantly reduced compared to normal group(P<0.05),while the medium and high-dose groups of GAPT intestinal absorption solution were significantly increased compared to model group(P<0.0001,P<0.001). There was no significant difference between pathway inhibitor group and model group(P>0.05).[Conclusion]GAPT intestinal absorption solution treats AD through multiple pathways and multiple targets,and the regulation of PI3K-AKT signaling pathway and its downstream targets is the key to its role.
