title: Eriodictyol Attenuates β-Amyloid 25-35 Peptide-Induced Oxidative Cell Death in Primary Cultured Neurons by Activation of Nrf2.
abstract: 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 β-amyloid 25-35 peptide (Aβ25-35)-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 μM Aβ25-35 in the absence or presence of eriodictyol (20, 40 and 80 μM). The results revealed that Aβ25-35-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 Aβ25-35-induced cell death partially through Nrf2/ARE signaling pathway, which further supports that eriodictyol might be a promising novel therapeutic agent for AD.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jing
authors.forename: Huanying
authors.initials: H
authors.lastname: Shi
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhu
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Manru
authors.initials: M
authors.lastname: Ren
authors.forename: Minxing
authors.initials: M
authors.lastname: Han
authors.forename: Dongmei
authors.initials: D
authors.lastname: Ren
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lou
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D044950:Flavanones / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000633:toxicity*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D044950:Flavanones; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C007619:eriodictyol