Targeting amyloid aggregation with ethanol extracts of fermented Swietenia macrophylla: a metabolomic and molecular docking approach

Abstract

Microbial fermentation offers a promising yet underexplored strategy to enhance the anti-amyloidogenic potential of phytochemicals. In particular, the anti-aggregation mechanism of fermented Swietenia macrophylla (mahogany) seed extracts against amyloidogenic proteins has not been comprehensively elucidated. Therefore, this study aimed to evaluate the anti-amyloidogenic potential of mahogany seed extracts fermented with Aspergillus niger (A. niger) using integrated in vitro and in silico approaches. Fermented extracts were analyzed for changes in secondary metabolites and tested for protein aggregation inhibition under thermal and DTT-induced stress using BSA models. LC-MS profiling and molecular docking on Aβ42 were conducted to identify key active compounds and interaction mechanisms. Fermentation significantly elevated triterpenoids (179%), flavonoids (130%), and phenolics (4%), leading to inhibition of BSA aggregation (57.12–79.09%) compared to quercetin (43.24–44.44%). LC-MS identified myricetin, gallocatechin, swietenolide, and swietenine as dominant metabolites. Docking and dynamic simulations revealed that flavonoids (−6.1 to −6.2 kcal/mol) stabilized critical Aβ42 residues (PHE19–ILE31) and reduced residue fluctuations (3.1–4.7 Å), while limonoids contributed to early aggregation inhibition despite higher flexibility (> 6 Å). These findings demonstrate, for the first time, that A. niger fermentation synergistically enhances the anti-amyloidogenic efficacy of mahogany seed metabolites, suggesting their potential as natural neurodegenerative agents against amyloidosis.
Keywords: Anti aggregation, fermented, Swietenia macrophylla, in vitro, in silico