Exploration of the mechanism of fraxetin in treating acute myeloid leukemia based on network pharmacology and experimental verification.
Heliyon
; 10(15): e34717, 2024 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-39166080
ABSTRACT
Objective:
To explore the pharmacological mechanism of the effect of fraxetin in treating acute myeloid leukemia (AML) by the network pharmacology method combined with experimental validation.Methods:
The targets of fraxetin were identified through Swisstarget prediction, PhammerMap, and CTDBASE. Disease-related targets of AML were explored using GeneCards and DisGenet databases, and the intersected targets were analyzed in the String website to construct a protein-protein interaction (PPI) network. Subsequently, gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted using the DAVID database. Molecular docking of core proteins with drugs was performed using Auto Dock Vina software. Finally, the effect of fraxetin on AML was evaluated by in vitro experiments. The effect of fraxetin on AML cell proliferation was assessed by CCK8, the effect of fraxetin on AML cell apoptosis was assessed by flow cytometry, and the expression of relevant protein targets was detected by Western blotting to evaluate the anti-AML effect of fraxetin.Results:
In this study, fraxetin exerts its effect against AML through 101 intersecting genes. The pathway enrichment analysis revealed that the pharmacological effects of fraxetin on AML were related to the Adenosine 5'-monophosphate (AMP)-activated protein kinase ï¼AMPKï¼ signaling pathway, and the molecular docking results indicated that fraxetin had an excellent binding affinity to both the core target and AMPK. In vitro experiments have demonstrated that fraxetin inhibited the proliferation and induced apoptosis of THP1 and HL60 cells, and the western blotting results indicated that the p-AMPK of the fraxetin intervention group was significantly changed in a dose-dependent manner.Conclusion:
Fraxetin may modulate the AMPK signal pathway by interactine with the core target, thereby potentially therapeutic effect on AML.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Heliyon
Year:
2024
Document type:
Article