Lee_2025_J.Sci.Food.Agric__

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss, with oxidative stress and neuroinflammation playing crucial roles in its progression. Current treatments, such as acetylcholinesterase (AChE) inhibitors, offer limited symptomatic relief and can have side effects. With growing interest in functional foods that have fewer side effects, pomegranate (Punica granatum L.) has gained attention because of its rich antioxidant content. The present study aims to evaluate the antioxidant and neuroprotective effects of four pomegranate cultivars: 'Wonderful', 'Phoenicia', 'Azadi' and 'Eversweet'. Additionally, it investigates their metabolite profiles and predicts potential bioactive compounds that could help prevent AD. RESULTS: The 'Wonderful' cultivar demonstrated the highest levels of total phenolic content, total flavonoid content, total anthocyanin content and radical scavenging activities. The AChE and butyrylcholinesterase (BuChE) inhibition rates were highest in 'Phoenicia' and 'Wonderful' cultivars, suggesting potential neuroprotective effects. PC12 cell assays indicated that these cultivars significantly improved cell viability, reduced reactive oxygen species and malondialdehyde levels, and also enhanced catalase activity. Metabolomics analysis identified 141 metabolites, with the 'Wonderful' cultivar showing the highest metabolite abundance. Molecular docking studies indicated that some metabolites, such as taxifolin, demonstrated strong binding affinities for AChE and BuChE, suggesting potential for AD treatment. CONCLUSION: The 'Wonderful' and 'Phoenicia' cultivars demonstrated the most promising antioxidant and neuroprotective effects among the evaluated pomegranates, likely because of their high taxifolin content. These findings suggest that these cultivars could be valuable for developing functional foods aimed at AD prevention and treatment. 2025 Society of Chemical Industry.