The neuroprotective effects of phytoestrogen α-zearalanol on β-amyloid-induced toxicity in differentiated PC-12 cells

Although favorable effects of estrogen replacement therapy on Alzheimer's disease on postmenopausal women have been recognized, an associated increased incidence of uterine and breast tumors has jeopardized the clinical use of estrogen. Phytoestrogen alpha-zearalanol (alpha-ZAL) is a reductive product of the Gibberella zeae metabolite and abundant in plants and vegetables, which has been shown to protect cell injury with low side-effects on uterine and breast. This study was designed to evaluate the neuroprotective effects of alpha-ZAL, on the cultured differentiated PC-12 cells, while 17 beta-estradiol (17 beta-E2) has been used as an estrogen positive control. Following a 24 h exposure of the cells to amyloid beta-peptide fragment 25-35 (A beta(25-35)), a significant reduction in cell survival and activities of total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as increased of malondialdehyde (MDA) were observed. However, preincubation of the cells with alpha-ZAL or 17 beta-E2 prior to A beta(25-35) exposure elevated the cell survival and SOD and GSH-Px activities, and decreased the level of MDA. In addition, A beta(25-35) caused a significant cell apoptosis and increased apoptotic rate, accompanied by decreasing of bcl-2 expression and increasing bax, caspase-3 expression, pretreatment of the cells with alpha-ZAL or 17 beta-E2 ameliorated these changes induced by A beta(25-35). Taken together, these data indicated that the phytoestrogen alpha-ZAL may effectively antagonize A beta(25-35)-induced cell toxicity by attenuating oxidative stress and apoptotic cell death, in a manner similar to 17 beta-E2. Our results suggested that alpha-ZAL can be used as a potential substitute of 17 beta-E2 in postmenopausal women for Alzheimer's disease prevention. (C) 2011 Elsevier B.V. All rights reserved.