Schisandrin A, a dietary lignan from Schisandra chinensis, ameliorates cognitive deficits in AlCl₃/D-galactose-treated mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Chronic aluminum exposure, a well-recognized environmental risk factor, exacerbates AD pathogenesis by driving oxidative stress and neuroinflammation. Schisandrin A (SchA), a bioactive lignan from the medicinal and edible plant Schisandra chinensis, exhibits promising antioxidant and anti-inflammatory properties, yet its nutritional relevance for AD intervention remains undefined. This study evaluated SchA's neuroprotective potential in an AlCl₃/D-galactose-induced cognitive impairment model. We found that SchA significantly ameliorated learning and memory impairments in Morris water maze, novel object recognition, open field and Y-maze tests, alleviated neuronal damage in the hippocampus and cortex, and reduced cerebral amyloid-β (Aβ) production in AlCl₃/D-galactose-treated mice. Mechanistically, SchA mitigated neuroinflammation via inhibiting the IKK/NF-κB/iNOS pathway, and alleviated oxidative stress through activating the Nrf2/HO-1 axis. Our findings demonstrate that SchA exerts neuroprotective effects in AlCl₃/D-galactose-treated mice, accompanied by modulation of inflammatory and oxidative-stress-related signalling, supporting its potential as a nutritional intervention for AD.