de Oliveira_2025_J.Pharm.Pharmacol__

OBJECTIVES: Mangiferin, a chemical constituent of Mangifera indica, has been the subject of extensive investigation due to its diverse biological activities, as detailed in numerous scientific studies. Its aglycone, norathyriol, has similarly garnered attention from researchers. In furtherance of our ongoing research goals, this article presents an evaluation of these compounds in relation to biomarkers associated with Alzheimer's disease. METHODS: The inhibition of acetylcholinesterase (AChE) and beta-secretase (BACE-1), as well as the aggregation of the amyloid beta (Abeta)42 peptide, was assessed using Ellman's colourimetric method, fluorescence resonance energy transfer (FRET), and thioflavin-T fluorescence emission, respectively. KEY FINDINGS: Mangiferin exhibited no inhibitory effect on AChE, whereas norathyriol demonstrated an inhibitory concentration (IC50) of 6.23 microM. Molecular docking revealed that the mangiferin-AChE and mangiferin-BACE-1 complexes did not interact with sites related to enzyme activity. In contrast, norathyriol showed favourable interactions with Asp72 at the peripheral site of AChE and formed significant interactions with BACE-1 through hydrogen bonds, as suggested by molecular docking. The IC50 of norathyriol for BACE-1 inhibition was found to be 9.75 microM. The reduction in Abeta42 aggregation by norathyriol was only 28%. CONCLUSION: We conclude that norathyriol is a promising prototype for drug development aimed at treating Alzheimer's disease.