Exploring the neuroprotective effects of Pterostilbene against rotenone-induced Parkinson's disease in Zebra Fish: An integrated in silico and in vivo approach

Purpose: To investigate the neuroprotective potential of pterostilbene (a natural dietary compound found primarily in blueberries and other small fruits) against rotenone-induced Parkinson's disease (PD) in zebrafish. Methods: Rotenone-induced Parkinson’s disease was modeled in adult male Zebrafish using 5 μg/L rotenone via static immersion for 21 days. Pterostilbene was co-administered at 125 μg/L and 250 μg/L. Molecular docking was used to assess the affinity of pterostilbene for monoamine oxidase (MAO), while molecular dynamics evaluated the complex stability. Behavioral tests and biochemical analyses were conducted on day 22 to assess neuroprotection. Results: Treatment with pterostilbene significantly enhanced locomotor activity and reduced anxiety-like behaviors in Zebrafish exposed to rotenone (p < 0.0001). Also, pterostilbene significantly inhibited dopaminergic neuronal degeneration and neuroinflammation in a dose-dependent manner (p < 0.001). Conclusion: Pterostilbene significantly enhances motor activity, reduces anxiety-like behaviours, inhibits dopaminergic neuronal degeneration, and inflammation. Further studies into the kinetics of pterostilbene and adjusted dosing regimens would be required before clinical trials.