Sesaminol Glucosides의 기억력 회복능 및 β,γ-Secretase 활성에 미치는 영향

Protective Effect of Sesaminol Glucosides on Memory Impairment and β,γ-Secretase Activirt In Vivo

Alzheimers disease(AD) is the most prevalent form of neurodegenerations associated with aging in human population. This disease is characterized by the extracellular deposition of beta-amyloid(Aβ)peptide in cerebral plaques. The Aβ peptide is derived from the β-amyloid precursor(Βapp). Photolytic processing of Βapp by β-secretase(beta-site APP-cleaving enzyme, BASE) and γ-secretase generates the Aβ peptide. Aeveral lines of evidence support that Aβ-induced neuronal cell death is major mechanisms od development of AD. Accordingly, the β-and γ-secretase have been implicated to be excellent targets for the treatment of AD. We previously found that sesaminol glucosides have improving effect on memory functions through anti-oxidative mechanism. In this study, to elucidate possible other mechanism (inhi- bition of β- and γ-secertase) of sesaminol glucosides, we examined the improving effect of sesaminol glucosides in the sco- polamine (1 mg/kg/mouse)-induced memory dysfunction using water maze test in the mice. Sesaminol glucosides (3.75, 7.5 mg/kg/6ml/day p.o., for 3 weeks) reversed the latency time, distance and velocity by scopolamine in dose dependent manner. Next, β- and γ-secertase were determined in different regions of brain. Sesaminol glucosides dose-depen- dently attenuated scopolamine-induced β-sectretase activities in cortex and hippocampous and γ-secertase in cortex. This study therefore suggests that sesaminol glucosides may be a useful agent for prevention of the development or progression of AD, and its inhibitory effect on secretase may play a role in the improving action of sesaminol glucosides on memory function.