Neuroprotective role of hesperidin against aluminium-induced neurotoxicity: evidence from behavioural changes and suppression of inflammatory and oxidative markers

Chronic aluminium exposure is an established environmental risk factor for cognitive decline, acting largely through oxidative injury and glial-driven inflammation in the brain. Hesperidin, a citrus flavanone glycoside with reported antioxidant and anti-inflammatory activity, was examined for protection against aluminium chloride (AlCl₃) neurotoxicity. Male Swiss albino mice ( n = 5 per group) received AlCl₃ alone or AlCl₃ together with hesperidin at 50 or 100 mg/kg by oral gavage for 28 days, alongside a vehicle-treated control. Spatial working memory and exploratory behaviour were assessed using the Y-maze and open field tests, and brain tissue was analysed for superoxide dismutase (SOD), catalase, glutathione S-transferase (GST), malondialdehyde (MDA), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α). AlCl₃ produced consistent behavioural impairment, with reduced rearing and line crossing, prolonged centre-square duration, and a fall in correct Y-maze alternation by day 28 compared to control ( p < 0.05). Total arm entries were not significantly reduced by AlCl₃, indicating that the alternation deficit did not reflect altered exploratory activity. These deficits were accompanied by depleted SOD, catalase, and GST activity, elevated MDA, and pronounced increases in IL-1β and TNF-α. Hesperidin reversed this profile in a dose-related manner. The 100 mg/kg dose significantly restored line crossing and Y-maze alternation, shortened centre-square duration, raised antioxidant enzyme activity, lowered lipid peroxidation, and suppressed both cytokines compared to the AlCl₃-only group ( p < 0.05), while the lower dose produced intermediate effects. These findings indicate that hesperidin protects the mouse brain against aluminium-induced cognitive and biochemical damage, with behavioural recovery accompanied by reinforcement of endogenous antioxidant enzyme activity and reduction of pro-inflammatory cytokine levels. The upstream signalling responsible was not measured in this study, and the findings support further preclinical evaluation rather than any claim of therapeutic potential.