Unravelling the neuroprotective effects of taxifolin against scopolamine-induced dementia in male Sprague Dawley rats: A comprehensive preclinical investigation

• Scopolamine administration in rats resulted in dementia, cognitive decline, increased myeloperoxidase activity, neuronal death, oxidative stress (augmented lipid peroxidation and nitrite) and dysfunction of antioxidant mechanisms (superoxide dismutase, catalase, and reduced glutathione). • Pre-treatment with taxifolin in rats ameliorated behavioural, neurochemical, and histopathological consequences of scopolamine administration. • Scopolamine administration in rats resulted in increased acetylcholinesterase activity. On the contrary, the administration of taxifolin followed by scopolamine in rats mitigated the scopolamine-induced increased acetylcholinesterase activity. • Taxifolin showed a docking score of 55 against the acetylcholinesterase. • Taxifolin was shown to have relatively acceptable properties by ADMET findings based on structure to activity computation linked to pharmacokinetics and toxicity evaluation. Alzheimer's disease is a neurodegenerative disorder which impacts millions of individuals worldwide, is driven by cholinergic neuron degeneration. The current research examined taxifolin's neuroprotective effects against scopolamine-induced dementia in rats. Twenty male Sprague-Dawley rats were assigned into four groups (5 rats/group). Group I (control group) and Group II (disease group) received saline intraperitoneally for five days. Group III (treatment group) received taxifolin (5 mg/kg, i.p. ) for five days. Group IV (positive control) received donepezil (2 mg/kg, i.p. ) for five days. Except Group I all the other Groups received scopolamine (2 mg/kg, i.p. ) on day five. Cognitive abilities were evaluated using the Y-maze, Morris water maze, and Cook's pole climbing tests. Post-euthanasia, brain samples were analysed for acetylcholinesterase activity, oxidative stress markers (lipid peroxidation, nitrite levels), antioxidant enzymes (superoxide dismutase, catalase, reduced glutathione), and inflammation (myeloperoxidase activity). Molecular docking was performed to evaluate taxifolin's binding with acetylcholinesterase. In silico studies were done to analyse pharmacokinetic and toxicological properties of taxifolin. Scopolamine caused memory impairment, altered the brain's histopathology, increased acetylcholinesterase activity, lipid peroxidation, nitrite levels, and myeloperoxidase activity, while altering antioxidant enzymes. Taxifolin pre-treatment reversed these alterations, improving cognitive function, reducing oxidative stress and inflammation, and restoring antioxidant enzymes. Molecular docking showed taxifolin inhibited acetylcholinesterase with a docking score of 55, while in silico studies revealed favourable pharmacokinetic and toxicological profiles. Taxifolin effectively mitigates scopolamine-induced cognitive and biochemical impairments, suggesting its potential as a therapeutic candidate for Alzheimer's disease. Further studies are required to validate these findings.