Neuroprotective effects of nobiletin and tangeretin against amyloid β1-42-induced toxicity in cultured primary rat neurons

Background Amyloid beta (A beta)-induced oxidative stress and neurotoxicity play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we evaluated the neuroprotective effects of nobiletin and tangeretin against A beta-induced neurotoxicity in primary rat neurons. Methods The protection of nobiletin and tangeretin against A beta(1-42) toxicity on primary cortical neurons was determined by the MTT assay. The free radical scavenging ability of nobiletin and tangeretin was evaluated by measuring the intensity of dichlorodihydrofluorescein (DCF) fluorescence. The protective effects of nobiletin and tangeretin against A beta(1-42)-induced neurotoxicity were further evaluated by the western blot and thioflavin T binding assay. Results Nobiletin (1, 5, 12.5, 25, 50 mu M) and tangeretin (1, 5, 12.5, 25 mu M) significantly decreased A beta-induced neurotoxicity in a concentration-dependent manner (P < 0.05 or P < 0.01). The cell viability of neuronal cells decreased to 68.5% by treatment of A beta(1-42) (1 mu M). The highest cell viability (81.4%) of nobiletin treatment group was found at the concentration of 50 mu M. Meanwhile, tangeretin possessed the highest neuroprotective effect at the concentration of 25 mu M in which the cell viability was 88.9%. In addition, nobiletin and tangeretin effectively suppressed A beta-induced intracellular oxidative stress (P < 0.05). Tangeretin also significantly reduced the aggregation of A beta(1-42) monomer (P < 0.01), while aggregation of A beta(1-42) was not significantly inhibited by treatment with nobiletin. Conclusion Both nobiletin and tangeretin significantly decreased A beta(1-42)-induced neurotoxicity. Tangeretin significantly reduced the aggregation of A beta(1-42), while the neuroprotective effect of nobiletin was due to the reduction of oxidative damage. The results suggested that tangeretin and nobiletin might be a potential neuroprotective food ingredient.