Protective effect of puerarin against beta-amyloid-induced oxidative stress in neuronal cultures from rat hippocampus: involvement of the GSK-3β/Nrf2 signaling pathway.

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.