Exploring the action mechanisms of Areca catechu L against diabetes mellitus with neurodegenerative diseases using network pharmacology and experimental verification
Objective:To study the effects of Areca catechu L(AC)on lowering blood glucose and stimulating central ner-vous system.The potential effects on the treatment of diabetes mellitus(DM)and neurodegenerative diseases(NDs)were investi-gated by means of network pharmacology.Methods:In this study,the main active components and target genes of AC were ob-tained by screening databases and literature.Disease target genes related to DM and NDs were obtained using GeneCards and oth-er databases.Common target gene ontology(GO)and signaling pathway(KEGG)were enriched with Rstudio,and common tar-get protein interaction network(PPI)was constructed with STRING11.5 online database.Molecular docking was used to observe the binding ability of the main active component(ligand)of AC to the core target(receptor).CCK8 was used to detect the effects of different concentrations of arecoline on cell viability to determine the dose concentration.The effect of arecoline on extracellular glucose content was detected with glucose detection kit,and the efficacy of arecoline in improving DM by regulating glucose me-tabolism was evaluated.Results:Network pharmacological analysis showed that AKT1,TP53,PPARG and PI3K-Akt signaling pathway were the core targets and pathways for AC to improve DM and NDs.Molecular docking results also showed that the ac-tive components of AC had high binding ability with the core targets of DM and NDs.The results of CCK8 experiment showed that the cell proliferation ability was the highest when arecoline was given 0.5 mg/mL and stimulated for 24 h(P<0.01).0.5 mg/mL,1 mg/mL arecoline concentration increased the glucose uptake of cells(P<0.01),and 0.5 mg/mL arecoline dose has the best efficacy.Conclusion:Areca nut may improve DM and NDs by regulating AKT1,TP53,PPARG and PI3K-Akt signaling pathway.Arecoline has obvious effect on cell proliferation and glucose metabolism.
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