Wolffia globosa -derived nanovesicles as a natural source of bioactive metabolites with neuroprotective potential against methylglyoxal-induced oxidative stress

Plant-derived nanovesicles (PDNVs) have attracted increasing attention for their potential biomedical applications, particularly in oxidative stress-related diseases and neuroprotection. Wolffia globosa, an emerging functional food and potential future food source, is rich in phytochemicals associated with health-promoting properties. Harnessing W. globosa-derived nanovesicles (WGNVs) represents a promising strategy for expanding the biomedical applications of this plant. In this study, WGNVs were isolated and characterized, and their neuroprotective potential was evaluated in vitro. The isolated WGNVs exhibited nanoscale dimensions and a lipid bilayer structure. Biochemical analyses revealed substantial total phenolic and flavonoid contents, alongside intrinsic antioxidant activities. Untargeted metabolomic profiling identified a diverse repertoire of metabolites, including major constituents subsequently validated using independent analytical approaches. These findings provided a foundation for investigating the neuroprotective effects of WGNVs in a methylglyoxal (MGX)-induced model of neuronal oxidative stress. High-resolution confocal microscopy demonstrated the cellular localization of WGNVs within neuronal cells, providing evidence of interactions between plant-derived nanovesicles and neuronal cells. WGNV treatment attenuated MGX-induced free radical accumulation and oxidative stress responses while preserving cellular morphology integrity. Collectively, this study provides foundational evidence of the physicochemical characteristics, metabolite composition, and in vitro neuroprotective potential of WGNVs. These findings highlight WGNVs as a promising naturally derived nanocarrier platform for investigating plant-animal interkingdom interactions and exploring potential therapeutic applications across a broad range of biomedical fields.