Protective effects of alkaloidal fraction of Elaeocarpus angustifolius Blume against AlCl₃-evoked neurotoxicity: insights from an in vivo model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal degeneration. Current treatments offer limited efficacy. Elaeocarpus angustifolius Blume (Rudraksha), used traditionally in Ayurveda for neurological disorders, has shown potential for cognitive health, warranting investigation in AD models. This study aimed to evaluate the neuroprotective efficacy of an alkaloid-rich fraction of E. angustifolius (EAF) in an AlCl₃-induced rat model of AD. AD-like symptoms were induced by oral administration of AlCl₃ (100 mg/kg) for 60 days, followed by a 30-day oral treatment with EAF (200 and 400 mg/kg). Cognitive performance was assessed using the Morris water maze, elevated plus maze, novel object recognition, and locomotor activity tests. Biochemical and molecular markers were analysed, and hippocampal histopathology was conducted. AlCl₃ exposure caused significant cognitive and motor deficits, elevated Aβ1-42 and phosphorylated tau, decreased acetylcholine and dopamine, increased glutamate and NF-κB, and reduced NRF-2 expression, indicating oxidative stress and neuroinflammation. EAF treatment significantly improved behavioral outcomes, reduced Aβ1-42 and tau levels, restored neurotransmitter balance, enhanced antioxidant markers (GSH, SOD, CAT), and reduced MDA. It suppressed NF-κB and upregulated NRF-2, suggesting antioxidant and anti-inflammatory effects. Histopathological analysis confirmed hippocampal neuroprotection. EAF exhibited significant neuroprotective effects by mitigating oxidative stress, neuroinflammation, and AD-related pathologies, including amyloid accumulation and cholinergic dysfunction. These findings support the potential of EAF as a therapeutic candidate for AD prevention and management.