Eriodictyol Attenuates β-Amyloid 25-35 Peptide-Induced Oxidative Cell Death in Primary Cultured Neurons by Activation of Nrf2

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre, has long been established as an antioxidant. The present study was designed to investigate the effect of eriodictyol on beta-amyloid 25-35 peptide (A beta(25-35))-induced oxidative cell death in primary neurons and to explore the role of the nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in this process. For this purpose, primary cultures of cortical neurons were exposed to 15 mu M A beta(25-35) in the absence or presence of eriodictyol (20, 40 and 80 mu M). The results revealed that A beta(25-35)-induced cytotoxicity and apoptotic characteristics such as activation of JNK/p38 apoptotic signaling pathway were effectively attenuated by eriodictyol pretreatment. Eriodictyol treatment also resulted in an increase in Nrf2 protein levels and subsequent activation of ARE pathway genes in primary cultured neurons. The protective effects of eriodictyol were attenuated by RNA interference-mediated knockdown of Nrf2 expression. Taken together, these results clearly demonstrate that eriodictyol protects neurons against A beta(25-35)-induced cell death partially through Nrf2/ARE signaling pathway, which further supports that eriodictyol might be a promising novel therapeutic agent for AD.