Natural Plant Extracts Rescue Memory Deficits in Drosophila Neurodegeneration Models

Neurodegenerative diseases are characterized by progressive impairments in cognition, stress resilience, and behavior, yet effective therapeutic interventions remain limited. Here, we performed a functional screening of Nicaraguan plant extracts using Drosophila melanogaster models of neurodegeneration-specifically Appl and DJ-1β mutants-to identify candidate extracts with neuroprotective potential. Flies were evaluated using a multi-assay pipeline that included memory testing, reactive oxygen species-induced survival assays, sleep analysis, locomotor performance, and mRNA expression profiling. Screening identified three plant extracts-Casearia corymbosa, Xylosma flexuosa, and Morisonia incana-that significantly improved memory performance in DJ-1β mutants, whereas only partial memory recovery was observed in the Appl model, indicating genotype-dependent efficacy. None of the extracts rescued sleep defects in either disease model, suggesting limited influence on sleep-regulatory pathways. Notably, all three extracts significantly enhanced survival under oxidative stress in both Appl and DJ-1β mutants. In addition, C. corymbosa and M. incana significantly improved locomotor deficits in DJ-1β flies. Together, these findings demonstrate that Nicaraguan plant extracts exert selective and dissociable effects on cognitive function and oxidative stress resistance. In particular, M. incana emerges as a promising candidate for enhancing cellular stress resilience in neurodegenerative contexts. This work highlights the utility of Drosophila-based functional screening for identifying plant-derived compounds with targeted neuroprotective potential.