NEUROPROTECTIVE EFFECTS OF ZINGERONE ON OXIDATIVE STRESS-INDUCED NEURONAL APOPTOSIS FOLLOWING ALCL3/D-GALACTOSE ADMINISTRATION IN THE HIPPOCAMPUS OF MICE

This study aimed to evaluate the neuroprotective effects of Zingerone on Aluminium chloride (AlCl3) and D-Galactose (D-Gal)-induced oxidative stress and neurotoxicity in adult male Wistar mice. A total of twenty-eight mice were randomly assigned into four groups: Group 1 (Control), Group 2 (AlCl3/D-Gal), Group 3 (AlCl3/D-Gal + Zingerone), and Group 4 (AlCl3/D-Gal + Donepezil). AlCl3 and D-Gal were administered to induce oxidative stress, while Zingerone and Donepezil were used to assess their neuroprotective effects. After eight weeks of treatment, the animals were sacrificed, and brain tissues were collected for biochemical and immunohistochemical analysis. The activities of Superoxide Dismutase (SOD) and Catalase (CAT) were measured to determine the extent of oxidative damage, while Bcl2 expression in the hippocampus was evaluated using Immunohistochemistry to assess neuronal apoptosis. The AlCl3/D-Gal group showed significantly reduced SOD and CAT activities, indicating increased oxidative stress, along with decreased Bcl2 expression, suggestive of enhanced neuronal apoptosis. Conversely, Zingerone treatment significantly increased SOD and CAT activities and unregulated Bcl2 expression, indicating reduced oxidative stress and apoptosis. These effects were comparable to those observed in the Donepezil group, a standard neuroprotective agent. Behavioural and physical observations revealed that Zingerone-treated animals exhibited reduced neurological symptoms, improved weight gain, and restored normal behaviour compared to the AlCl3/D-Gal group. Statistical analysis using one-way ANOVA followed by Tukey’s post hoc test confirmed that the results were significant at p < 0.05. Overall, this study suggests that Zingerone has potent antioxidative and anti-apoptotic properties that mitigate AlCl3/D-Gal-induced neurotoxicity. Zingerone’s neuroprotective effects were comparable to Donepezil, highlighting its potential as a therapeutic agent for neurodegenerative disorders associated with oxidative stress and apoptosis, such as Alzheimer’s disease.