Acteoside and Isoacteoside Protect Amyloid ß Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo.

ABSTRACT

Acteoside and isoacteoside, two phenylethanoid glycosides, coexist in some plants. This study investigates the memory-improving and cytoprotective effects of acteoside and isoacteoside in amyloid ß peptide 1-42 (Aß 1-42)-infused rats and Aß 1-42-treated SH-SY5Y cells. It further elucidates the role of amyloid cascade and central neuronal function in these effects. Acteoside and isoacteoside ameliorated cognitive deficits, decreased amyloid deposition, and reversed central cholinergic dysfunction that were caused by Aß 1-42 in rats. Acteoside and isoacteoside further decreased extracellular Aß 1-40 production and restored the cell viability that was decreased by Aß 1-42 in SH-SY5Y cells. Acteoside and isoacteoside also promoted Aß 1-40 degradation and inhibited Aß 1-42 oligomerization in vitro. However, the memory-improving and cytoprotective effects of isoacteoside exceeded those of acteoside. Isoacteoside promoted exploratory behavior and restored cortical and hippocampal dopamine levels, but acteoside did not. We suggest that acteoside and isoacteoside ameliorated the cognitive dysfunction that was caused by Aß 1-42 by blocking amyloid deposition via preventing amyloid oligomerization, and reversing central neuronal function via counteracting amyloid cytotoxicity.