Objective β-amyioid peptides (Aβ) induced eerebrovascular dysfunction has been recognized as a vital factor involved in the pathogenesis of neurodegeneration.Genistein has antioxidative properties to prevent neurodegeneration induced by β-amyloid peptides.In this study,we tried to investigate whether genistein could antagonize oxidative damage induced by β-amyloid peptide 25-35 (Aβ25-35) in bEND.3 cells,and also identify the potential neuroprotective targets of genistein.Methods The bEND.3 cells were pre-incubated with/out genistein or vitamin E(Vit E) for 2 h followed by the incubation with Aβ25-35 (25 μM) for another 24 h.Vit E was used as the positive control.The laser scanning confocal fluorescence micrological technique was used in the measurement of reactive oxygen species (ROS).Cell redox state was measured by the enzymatic kits.Western Blot and RT-PCR were used to test the mRNA or protein expressions of the factors on NF-E2-related factor 2 (Nrf2) signaling pathway.The protein expression of nitrotyrosine in cells was also detected in this study.Results The results showed that genistein alleviated the increase of ROS and nitrotyrosine production induced by Aβ25-35,and maintained bEND.3 cell redox state by increasing GSH level and GSH/GSSG.Genistein could reverse the down-regulation of total protein and mRNA expressions of Nrf2,nuclear Nrf2,γ-glutamylcysteine synthetase (γ-GCS),phosphatidylinositol 3-kinase (PI3K) induced by Aβ25-35;while PI3K inhibitor LY294002 could attenuate the activation effects of genistein on Nrf2,especially for the promotion of its nuclear translocation.Conclusion These results suggested that genistein could protect cerebrovascular endothelial cells from Aβ25-35-induced oxidative damage.The potential mechanisms might be associated with the activation of Nrf2 signaling pathway by modulating PI3K activity.