title: Protective effect of puerarin against beta-amyloid-induced oxidative stress in neuronal cultures from rat hippocampus: involvement of the GSK-3β/Nrf2 signaling pathway.
abstract: Current evidence suggests that amyloid beta (Aβ) peptides may play a major role in the pathogenesis of Alzheimer's disease in part by eliciting oxidative stress. Puerarin, a major isoflavone glycoside from Kudzu root (Pueraria lobata), has been reported to exert estrogen-like and antioxidant activities. The central hypothesis guiding this study is that puerarin will prevent or at least markedly attenuate Aβ(25-35)-induced excess production of reactive oxygen species (ROS) by interrupting glycogen synthase kinase-3β (GSK-3β) signaling. In this study, we demonstrate that pretreatment of primary hippocampal neurons with puerarin significantly reduced Aβ(25-35)-induced oxidative stress characterized by scavenging of ROS and inhibiting lipid peroxidation. Puerarin induced expression of nuclear Nrf2 protein, but not in the Nrf2 mRNA level, and increased heme oxygenase-1 (HO-1) levels at levels of transcription and translation. Puerarin-induced Serine 9 phosphorylation of GSK-3β was blocked by lithium chloride treatment in primary hippocampal neurons, indicating the participation of the GSK-3β inactivation. This protective effect was partially reversed when GSK-3β were blocked by the chemical inhibitors such as lithium chloride. These results suggest puerarin as a phytoestrogen with potential of a possible therapeutic agent in neurodegenerative diseases involving oxidative stress.
authors.affiliation: The Hub Laboratory, Qiqihar Medical University, Qiqihar, P.R. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zou
authors.forename: B
authors.initials: B
authors.lastname: Hong
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Dong
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007529:Isoflavones / 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 / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D007529:Isoflavones; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D051547:Heme Oxygenase-1; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C033607:puerarin