Al-Sawasany_2025_J.Biochem.Mol.Toxicol_39_e70290

Alzheimer's disease (AD) is the most common cause of dementia, a neurodegenerative disorder that progress overtime, which is best known for mood swings and loss of cognitive, behavioral and functional abilities. Quercetin is one of the most consumed flavonoids in the diet and has neuroprotective, anti-inflammatory and antioxidant effects. The purpose of this study was to assess the potential neurotherapeutic effect of quercetin and compare it with donepezil. 40 Wister male rats were used and separated into two main groups: Group I: control group; Group II: AD group, which was divided into four subgroups: Group IIA: untreated AD-rats; Group IIB: quercetin treated AD-rats; Group IIC: donepezil treated AD-rats and Group IID: combined group of quercetin and donepezil. Hydrated aluminum chloride (AlCl(3).6H(2)O) solution (75 mg/kg/day) was administered orally for 6 weeks to induce the AD-like conditions. Morris water maze, behavior test, was used to monitor the cognitive function. Hippocampal tissues were excised for assessment of Alzheimer's parameters and blood samples were obtained for liver and kidney function assessment. According to the final findings, untreated rats presented significantly increased levels of amyloid beta(1-42); tau protein; malondialdehyde; nuclear factor kappa-B; acetylcholinesterase activity, beta-site amyloid precursor protein cleaving enzyme 1 upregulation and miRNA-124 downregulation. The best results of treatment were observed in the combination of donepezil and quercetin, as revealed by histopathological observations via H&E and Congo red stains. This study led to the conclusion that quercetin, by targeting several pathogenic pathways, could be used as an adjuvant drug with donepezil for AD treatment.