Several lines of evidence support that
beta-amyloid (Abeta)-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 Abeta-induced oxidative cell death in cultured rat
pheochromocytoma (PC12) cells.
Sesaminol glucoside (50-250microg/ml) decreased Abeta(25-35)-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 (50-250microg/ml) also effectively decreased Abeta1-42 and ADDL form of Abeta1-42 as well as the combination of H2O2 with FeSO4-induced cell damages. In mechanistic study,
sesaminol glucosides attenuated Abeta25-35-induced activation of redox
transcription factor nuclear factor-kappaB NF-kappaB through inhibition of p50 translocation and IkappaB phosphorylation, and blocked
NF-kappaB-dependent
luciferase activity in addition to the inhibitory effect on Abeta25-35-induced activation of ERK
kinase signal pathway. Consistent with the inhibitory effect on Abeta25-35-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 Abeta25-35-induced ROS generation,
NF-kappaB activation and cell death were further enhanced with
glutathione. This study therefore suggests that
sesaminol glucosides have protective effect on Abeta-induced neuronal cell death, and its effect may be through antioxidative property.