Journal
FREE RADICAL RESEARCH
Volume 47, Issue 1, Pages 55-63Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10715762.2012.742518
Keywords
reactive oxygen species; heme oxygenase-1; Alzheimer's disease; antioxidant; amyloid beta
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Funding
- National Natural Science Foundation of China [81073080]
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Current evidence suggests that amyloid beta (A beta) 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 A beta(25-35)-induced excess production of reactive oxygen species (ROS) by interrupting glycogen synthase kinase-3 beta (GSK-3 beta) signaling. In this study, we demonstrate that pretreatment of primary hippocampal neurons with puerarin significantly reduced A beta(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-3 beta was blocked by lithium chloride treatment in primary hippocampal neurons, indicating the participation of the GSK-3 beta inactivation. This protective effect was partially reversed when GSK-3 beta 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.
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