Modulatory effects of hesperidin on rotenone-induced neurotoxicity in Drosophila melanogaster

Neurodegenerative disorders are closely associated with oxidative stress, mitochondrial dysfunction, and apoptosis. Rotenone, a potent inhibitor of mitochondrial complex I, is widely used to model Parkinson-like pathology because it induces oxidative damage and selective loss of dopaminergic neurons. In the present study, Drosophila melanogaster was employed to investigate rotenone-induced neurotoxicity and to evaluate the protective potential of hesperidin, a naturally occurring flavonoid known for its antioxidant and anti-apoptotic activities. Exposure to rotenone resulted in reduced survival rates, impaired locomotion and climbing ability, elevated reactive oxygen species (ROS) levels, increased protein oxidation, and heightened caspase-3 activity, reflecting neurodegenerative changes. Notably, co-treatment with hesperidin mitigated these adverse effects by enhancing motor performance, decreasing oxidative stress markers, and suppressing apoptotic signaling. Collectively, these findings suggest that hesperidin offers significant protection against rotenone-induced neurotoxicity in D. melanogaster, highlighting its potential as a therapeutic candidate for neurodegenerative disorders.