Neuroprotective effects of oleuropein on dopamine level and caspase-3 activity in zebrafish model of Parkinson’s disease

Background: Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, largely driven by oxidative stress-mediated apoptosis. Caspase-3 acts as the central executioner in this cell death pathway. While oleuropein, a phenolic compound from Olea europaea , is known for its antioxidant properties, its specific mechanism in modulating the caspase-3-dopamine axis in in vivo PD models remains to be fully elucidated. This study aimed to investigate the neuroprotective and neurorestorative effects of oleuropein isolate on brain dopamine levels and caspase-3 activity in a Rotenone-induced zebrafish ( Danio rerio ) model of PD. Methods: Thirty adult male zebrafish were randomized into five groups: Negative control, positive control (Rotenone induced), and three treatment groups (preventive, curative, and co-treatment) receiving oleuropein isolate (100 mg/kg). The PD model was established through rotenone induction to trigger mitochondrial dysfunction. Brain tissues were analyzed using specific enzyme-linked immunosorbent assay kits to quantify dopamine concentrations and caspase-3 activity. Data were analyzed using one-way analysis of variance followed by Tukey’s post hoc test. Results: Rotenone induction significantly elevated caspase-3 activity (29.74 ± 0.93 ng/mL) and depleted dopamine levels (20.67 ± 0.79 ng/mL) compared to controls ( p < 0.05), confirming apoptotic neurodegeneration. Oleuropein administration significantly reversed these pathological changes across all protocols ( p < 0.001). The co-treatment group exhibited the most potent suppression of caspase-3 (23.22 ± 0.50 ng/mL), while the curative group demonstrated the highest restoration of dopamine levels (25.31 ± 0.53 ng/mL), suggesting a compensatory neurorestorative mechanism. Conclusion: Oleuropein effectively mitigates dopaminergic neurodegeneration by inhibiting caspase-3-mediated apoptosis, which directly correlates with the functional restoration of brain dopamine levels. These findings support the potential of oleuropein as a therapeutic agent for preventing neuronal death and restoring dopaminergic function in PD.