Abstract
PURPOSE: Oxidative stress damage and impaired insulin receptor (IR) signaling are critical risk factors for contributing to cognitive impairment in Alzheimer's disease (AD) and other neurological disorders. The beta-amyloid peptide (Aβ) oligomer deposition in the hippocampal region decreases the IR expression. This study aimed to assess whether berries grown in Oman (Morus alba, Morus macroura, and Sideroxylon mascatense) could ameliorate dysfunction of the antioxidant system and restore the IR expression thereby improve the cognitive performance in aluminum chloride (AlCl(3)) induced AD mouse model. METHODS: Various biochemical assays were conducted to estimate antioxidant capacity. The total phenolic (TPC) and flavonoid (TFC) contents for the three varieties were quantified using Folin-Ciocalteu and AlCl(3) calorimetric methods, respectively. The antioxidant properties of the three berries were analyzed using thiobarbituric acid reactive substances assay (TBARS), superoxide dismutase assay (SOD), glutathione assay (GSH), glutathione peroxidase assay (GPx), and estimation of glutathione reductase (GR). Cognitive performance was measured using Morris water maze (MWM) and T-maze. FINDINGS: Berries, particularly M. alba and S. mascatense, demonstrated the highest phenolic and flavonoid content and exhibited strong antioxidant activity across all assays. Mice fed with M. alba, M. macroura, and S. mascatense showed better performance parameters in both MWM (spatial learning and memory) and T-maze (time taken to reach the platform) tests, along with enhanced IR signaling (p < 0.01). CONCLUSION: These findings suggest that supplementation with mulberries may improve cognitive decline and insulin resistance induced by AlCl(3), highlighting their potential as neuroprotective agents in AD.