Sesaminol glucosides protect β-amyloid induced apoptotic cell death by regulating redox system in SK-N-SH cells.

Abstract

We have investigated the neuroprotective effect of sesaminol glucosides (SG) in SK-N-SH cells. SG prevented apoptotic cell death induced by Aβ₂₅₋₃₅. In parallel, SK-N-SH cells exposed to Aβ₂₅₋₃₅ underwent oxidative stress as shown by the elevated level of intracellular ROS, lipid peroxidation, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, which were effectively suppressed by SG treatment. Furthermore, SG reversed the activities of catalase and glutathione peroxidase, and restored intracellular GSH levels in Aβ₂₅₋₃₅ challenged SK-N-SH cells. In addition, SG inhibited not only Aβ₂₅₋₃₅-induced apoptotic features including cleavage of poly(ADP-ribose) polymerase, activation of caspase-3, and activation of caspase-9, but also elevated Bax/Bcl-2 ratio in SK-N-SH cells treated with Aβ₂₅₋₃₅. It was also observed that Aβ₂₅₋₃₅ stimulated the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular protein regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase. SG inhibited phosphorylation of the JNK, ERK and p38 MAP kinase. These results suggest that SG has a protective effect against Aβ₂₅₋₃₅-induced neuronal apoptosis, possibly through scavenging oxidative stress and regulating MAPKs signaling pathways.