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

Brain disorders (Amsterdam, Netherlands) Pub Date : 2025-03-01 DOI:10.1016/j.dscb.2025.100203

Heena Chauhan , Bhavya Nakum , Udit Chaube , Bhagawati Saxena

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Abstract

Background/objective

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.

Methods

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.

Results

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.

Conclusion

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.

Abstract Image