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Vollständiger Abstract

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<h4>Background/aim</h4>Alzheimer's disease (AD) is a neurodegenerative disorder linked to cognitive decline and memory loss, marked by hyperphosphorylated tau tangles and decreased acetylcholine levels, which are affected by acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. Glycogen synthase kinase-3 beta (GSK-3β) also plays a role in AD through abnormal activation. In this study, the potential of β-arbutin to inhibit cholinesterases and GSK-3β was investigated, utilizing in vitro assays, cytotoxicity analysis, and molecular docking simulations to explore its therapeutic implications.<h4>Materials and methods</h4>Ellman's technique was used to test the inhibitory effects of arbutin on cholinesterase enzymes. An ATP-Glo luminescent assay kit was used to evaluate the inhibitory effects and inhibition kinetics of arbutin on GSK-3β. A Cell Titer-Glo 2.0 assay kit was used to assess the cytotoxicity of arbutin in SH-SY5Y cells.<h4>Results</h4>β-Arbutin exhibited significant inhibitory effects on AChE, BuChE, and GSK-3β, with IC 50 values of 0.6, 4, and 1.23 μM, respectively. The inhibition kinetics of GSK-3β with respect to ATP was competitive but with respect to the substrate (GS-2) was noncompetitive. We further found that β-arbutin, when applied alone to SH-SY5Y cells, does not affect cell viability and can ensure the sustainability of cell viability and health. Docking scores were -7.980, -6.726, and -6.115 kcal/mol for GSK-3β, AChE, and BuChE, respectively.<h4>Conclusion</h4>Our research demonstrates that arbutin is a modulator of cholinesterase and GSK-3β and may be beneficial as a multitarget-directed therapeutic natural compound for AD.

Abstract: PubMed · Datensatz