Effect of sesaminol glucosides on β-amyloid-induced PC12 cell death through antioxidant mechanisms

Several lines of evidence support that beta-amyloid (Aβ)-induced neurotoxicity is mediated through the generation of reactive oxygen species (ROS) and elevation of intracellular calcium. In this study, we have investigated protective effects of sesaminol glucosides on Aβ-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. Sesaminol glucoside (50-250 μg/ml) decreased Aβ25-35-induced ROS generation, formation of 8-oxodG, a form of oxidative DNA and elevation of intracellular calcium level concomitant with prevention of apoptotic cell death dose dependently. Sesaminol glucoside (50-250 μg/ml) also effectively decreased Aβ1-42 and ADDL form of Aβ1-42 as well as the combination of H2O2 with FeSO4-induced cell damages. In mechanistic study, sesaminol glucosides attenuated Aβ25-35-induced activation of redox transcription factor nuclear factor-κB (NF-κB) through inhibition of p50 translocation and IκB phosphorylation, and blocked NF-κB-dependent luciferase activity in addition to the inhibitory effect on Aβ25-35-induced activation of ERK kinase signal pathway. Consistent with the inhibitory effect on Aβ25-35-induced stress-induced cell death, sesaminol glucosides decreased expression of pro-apoptotic gene p53, and Bax and caspase-3, but enhanced expression of anti-apoptotic Bcl-2. Moreover, the protective effects of sesaminol glucoside on Aβ25-35-induced ROS generation, NF-κB activation and cell death were further enhanced with glutathione. This study therefore suggests that sesaminol glucosides have protective effect on Aβ-induced neuronal cell death, and its effect may be through antioxidative property.