Neuroprotective effects of nobiletin and tangeretin against amyloid β_1-42-induced toxicity in cultured primary rat neurons

Background: Amyloid β (Aβ)-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 Aβ-induced neurotoxicity in primary rat neurons. Methods: The protection of nobiletin and tangeretin against Aβ_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 Aβ_1-42-induced neurotoxicity were further evaluated by the western blot and thioflavin T binding assay. Results: Nobiletin (1, 5, 12.5, 25, 50 μM) and tangeretin (1, 5, 12.5, 25 μM) significantly decreased Aβ-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 Aβ_1-42 (1 μM). The highest cell viability (81.4%) of nobiletin treatment group was found at the concentration of 50 μM. Meanwhile, tangeretin possessed the highest neuroprotective effect at the concentration of 25 μM in which the cell viability was 88.9%. In addition, nobiletin and tangeretin effectively suppressed Aβ-induced intracellular oxidative stress (P < 0.05). Tangeretin also significantly reduced the aggregation of Aβ_1-42 monomer (P < 0.01), while aggregation of Aβ_1-42 was not significantly inhibited by treatment with nobiletin. Conclusion: Both nobiletin and tangeretin significantly decreased Aβ_1-42-induced neurotoxicity. Tangeretin significantly reduced the aggregation of Aβ_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.