Protective effect of quercetin in primary neurons against Aβ(1-42): relevance to Alzheimer's disease

Quercetin, a flavonoid found in various foodstuffs, has antioxidant properties and increases glutathione (GSH) levels and antioxidant enzyme function. Considerable attention has been focused on increasing the intracellular GSH levels in many diseases, including Alzheimer's disease (AD). Amyloid beta-peptide [A beta(1-42)], elevated in AD brain, is associated with oxidative stress and neurotoxicity. We aimed to investigate the protective effects of quercetin on A beta(1-42)-induced oxidative cell toxicity in cultured neurons in (lie present study. Decreased cell survival in neuronal cultures treated with A beta(1-42) correlated with increased free radical production measured by dichloro fluorescein fluorescence and an increase in protein oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (protein-bound 4-hydroxy-2-nonenal). Pretreatment of primary hippocampal cultures with quercetin significantly attenuated A beta(1-42)-induced cytotoxicity, protein oxidation, lipid peroxidation and apoptosis. A dose response study suggested that quercetin showed protective effects against A beta(1-42) toxicity by modulating oxidative stress at lower doses, but higher doses were not only non-neuroprotective but also toxic. These findings provide motivation to test the hypothesis that quercetin May Provide a promising approach for the treatment of AD and other oxidative-stress-related neurodegenerative diseases. (C) 2009 Elsevier Inc. All rights reserved.