Panaxydol and panaxynol protect cultured cortical neurons against Aβ25-35-induced toxicity

Amyloid beta protein (A beta), the central constituent of senile plaques in Alzheimer's disease (AD), is known to exert toxic effects on cultured neurons. In the present study, the protective effect of panaxydol (PND) and panaxynol (PNN) on A beta 25-35-induced neuronal apoptosis and potential mechanisms were investigated in primary cultured rat cortical neurons. Pretreatment of the cells with PND or PNN prior to 10 mu M A beta 25-35 exposure resulted significantly in elevation of cell survival determined by MTT assay, TUNEL/Hoechst staining and western blot. Furthermore, a marked increase in calcium influx and intracellular free radical generation was found after A beta 25-35 exposure, which could be almost completely reversed by pretreatment of PND or PNN. PND and PNN could also alleviate A beta 25-35-induced early-stage neuronal degeneration. These results indicated that inhibition of calcium influx and free radical generation is a mechanism of the anti-apoptotic action of PND and PNN. Since A beta plays critical roles in the pathogenesis of AD, these findings raise the possibility that PND and PNN reduce neurodegeneration in AD. (C) 2008 Elsevier Ltd. All rights reserved.