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 α-zearalanol (α-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 α-ZAL, on the cultured differentiated PC-12 cells, while 17β-estradiol (17β-E2) has been used as an estrogen positive control. Following a 24 h exposure of the cells to amyloid β-peptide fragment 25-35 (Aβ₂₅₋₃₅), 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 α-ZAL or 17β-E2 prior to Aβ₂₅₋₃₅ exposure elevated the cell survival and SOD and GSH-Px activities, and decreased the level of MDA. In addition, Aβ₂₅₋₃₅ 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 α-ZAL or 17β-E2 ameliorated these changes induced by Aβ₂₅₋₃₅. Taken together, these data indicated that the phytoestrogen α-ZAL may effectively antagonize Aβ₂₅₋₃₅-induced cell toxicity by attenuating oxidative stress and apoptotic cell death, in a manner similar to 17β-E2. Our results suggested that α-ZAL can be used as a potential substitute of 17β-E2 in postmenopausal women for Alzheimer's disease prevention.