Akbarizadeh-Mashkani_2025_Avicenna.J.Phytomed_15_1741

OBJECTIVE: Alzheimer's disease (AD) is a major public health concern. Berberine has shown promise in animal models by improving memory retention through multiple mechanisms. This study aimed to evaluate berberine therapeutic potential in ameliorating cognitive deficits in a rat AD model induced by intrahippocampal amyloid beta(1-42). MATERIALS AND METHODS: The AD model was induced through bilateral injection of amyloid beta(1-42) into the CA1 region of the hippocampus. Berberine was administered orally, starting one hour post-surgery for one week. Rats were divided into sham, amyloid beta, amyloid beta + berberine 10 mg/kg, and amyloid beta + berberine 50 mg/kg groups. The assessments encompassed cognitive testing and analysis of hippocampal markers, including oxidative stress, inflammation, apoptosis, and synaptic plasticity. Additionally, we evaluated acetylcholinesterase (AChE) activity and quantified neuronal loss in the hippocampal CA1 region. RESULTS: Berberine improved the cognitive performance of amyloid-microinjected rats in the Y-maze, novel object recognition, and passive avoidance tests in a dose-dependent manner. Berberine attenuated hippocampal levels of malondialdehyde (MDA), nitrite, and tumor necrosis factor alpha (TNFalpha). Furthermore, berberine improved the activity of superoxide dismutase (SOD) and reduced caspase-3 and AChE activity. Berberine also enhanced synaptophysin and microtubule-associated protein 2 (MAP2) levels and inhibited neuronal loss in the CA1 region. CONCLUSION: Berberine demonstrated protective effects against amyloid beta-induced cognitive deficits in a rat AD model, and these effects were associated with reduced oxidative and nitrosative stress, inflammation, apoptosis, and AChE activity, alongside enhanced synaptic protection.