A polysaccharide from Polygonatum sibiricum attenuates amyloid-β-induced neurotoxicity in PC12 cells

One of the pathological hallmarks of Alzheimer's disease (AD) is the progressive accumulation of betaamyloid (Ap) in the form of senile plaques, and A beta induced neurotoxicity has been identified as a major cause of the onset of AD. In this study, we investigated the protective effects of a polysaccharide (PS-WNP) from Polygonatum sibiricum against the A beta(25-35)-induced neurotoxicity in PC12 cells and explored the underlying mechanism. The results showed that pretreatment with PS-WNP significantly attenuated cell death and the elevated Bax/Bcl-2 ratio evoked by A beta(25-35), and subsequently inhibited mitochondrial dysfunction and cytochrome c release into the cytosol. Moreover, PS-WNP significantly inhibited A beta(25-35) induced caspase-3 activation and enhanced the protein levels of phosphorylated Akt (p-Akt) in PC12 cells. Additionally, pretreatment with the PI3K inhibitor (LY294002) completely abolished the protective effects of PS-WNP against A beta(25-35)-induced neuronal cell apoptosis. These observations unambiguously suggested that the protective effect of PS-WNP against A beta(25-35)-induced apoptosis in PC12 cells was associated with the enhancement of PI3K/Akt signaling pathway. (C) 2014 Elsevier Ltd. All rights reserved.