Quercetin Mitigates Aluminium Chloride-Induced Neurotoxicity by Modulating Oxidative Stress, Neuroinflammation, and Neurotransmitter Dysregulation in Rats

Memory impairment, characterized by reduced ability to recall facts, information, and experiences, is increasingly recognized as a major public health concern. This trend is largely driven by the rising prevalence of age-related cognitive decline and Alzheimer’s disease within the aging population. Aluminium chloride (AlCl□), a well-established neurotoxicant, induces neurobehavioral and biochemical alterations that mimic key features of neurodegenerative disorders, thus serving as a reliable experimental model for evaluating neuroprotective agents. This study assessed the neuroprotective efficacy of quercetin in a rat model of AlCl□-induced neurotoxicity. Fifty adult male rats (n = 10 per group) were randomly assigned into five groups. Neurotoxicity was induced by oral administration of AlCl□ (100 mg/kg/day) for 14 days. Subsequently, from days 14 to 35, rats received daily treatments of quercetin (100 or 200 mg/kg), donepezil (3 mg/kg), or vehicle control. AlCl□ exposure significantly impaired body weight gain, feed intake, locomotor activity, grooming behaviour, and spatial memory performance. Quercetin treatment markedly ameliorated these deficits, as evidenced by improved performance in Y-maze and radial-arm maze tasks. Biochemical analysis revealed that quercetin significantly reduced lipid peroxidation, enhanced total antioxidant capacity, and modulated inflammatory responses by decreasing pro-inflammatory cytokines (IL-1β, TNF-α) and elevating anti-inflammatory IL-10 levels. Furthermore, quercetin restored acetylcholine and brain-derived neurotrophic factor (BDNF) concentrations and preserved hippocampal cytoarchitecture, as demonstrated by histopathological assessment. These findings highlight quercetin’s therapeutic potential in mitigating aluminium-induced neurotoxicity and suggest its utility in the management of neurodegenerative disorders.