The neuroprotective effects of ipriflavone against H2O2 and amyloid beta induced toxicity in human neuroblastoma SH-SY5Y cells

Estrogenic compounds have been shown to have great potential for the treatment of Alzheimer's disease as demonstrated by its ability to antagonize amyloid beta peptide (A beta) induced toxicity, the hallmark of Alzheimer's disease. Key mechanisms include the involvements of both the antioxidant and the antiapoptotic pathways. However, side effects of estrogens, such as the increased incidence of breast cancer, are of concern for further clinical translation. Approaches to overcome such barriers include the structural modification of estrogenic compounds and the search of phytoestrogens, but these are a long way from being translated into the clinic. We identified a compound similar in structure to human estrogen-ipriflavone, an over-the-counter product marketed in the United States for the treatment or osteoporosis, efficiently antagonized AB induced toxicity. Use of a model with SH-SY5Y neural cells, we First demonstrated that iprillavone potently alleviated H2O2 induced cell death, reduced H2O2 induced elevations of both reactive oxygen species level and apoptosis. We extended our exploration of ipriflavone to All and observed similar effects. These protective effects were comparable to those produced by 17 beta-estradiol at similar concentrations. Caspase-3 inhibition, P beta K and MAPK activation were shown to be responsible for such antagonism of ipriflavone on All. Our results suggest that ipriflavone, a previously characterized compound, has great potential for expedited clinical translation for the treatment of Alzheimer's disease. (C) 2013 Elsevier By. All rights reserved,