D-(-)-ribofuranose identified from traditional fermented rice beverages of Assam exhibits monoamine oxidase inhibitory activity: an integrated GC-MS/MS metabolomics, molecular docking, molecular dynamics, and in vitro study.

UNLABELLED: Traditional rice-based fermented beverages are recognized as rich sources of bioactive metabolites with potential therapeutic relevance for neurodegenerative disorders. GC-MS/MS metabolomics, molecular modeling, and in vitro assays were combined to identify and evaluate metabolites with potential monoamine oxidase inhibitory activity and a preliminary approach to identify potential anti-Alzheimer's compounds from traditional rice beverages. GC-MS/MS-based untargeted metabolomics revealed substantial metabolic diversity, with 166, 113, 145, and 123 metabolites detected in black rohi (BR), sai mod (SM), jou bidwi (JOU), and rohi (RH), respectively, and 93 metabolites shared across the fermented samples. Structure-based virtual screening of 99 compounds comprising metabolites and FDA compound, identified D-(-)-ribofuranose as a candidate metabolite showing favorable predicted interactions with MAO-A and MAO-B in molecular docking studies of - 9.5 kcal/mol (MAO-A) and - 10.2 kcal/mol (MAO-B) compared to the reference drug isocarboxazid (- 7.2 and - 7.6 kcal/mol, respectively). Molecular dynamics simulations conducted for 200 ns confirmed structural stability of the complexes, with the MAO-B-D-(-)-ribofuranose system showing low RMSD (0.26 ± 0.03 nm), stable radius of gyration (2.19 ± 0.02 nm), solvent-accessible surface area values comparable to those observed for the reference complex (195 ± 6 nm2), and increased hydrogen bonding (5.6 ± 1.2 bonds). Cytotoxicity evaluation using the SH-SY5Y cell line yielded an IC50 value of 51.33 µM after 24 h exposure. Enzyme kinetics confirmed concentration-dependent inhibition of both MAO-A and MAO-B enzymes under the experimental conditions evaluated, supporting the potential of D-(-)-ribofuranose as a candidate monoamine oxidase inhibitory metabolite warranting further biochemical and pharmacological investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00720-6.