L-3-n-Butylphthalide ameliorates β-amyloid-induced neuronal toxicity in cultured neuronal cells

L-3-n-Butylphthalide (L-NBP), as an anti-cerebral ischemia agent, has been shown to have therapeutic effects on learning and memory deficits induced by chronic cerebral hypoperfusion and A beta intracerebroventricular infusion in rats. In the present study, we investigated the neuroprotective effects of L-NBP on beta-amyloid (A beta)(25-35)-induced neuronal death/apoptosis and potential mechanisms in rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. A beta(25-35) significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that A beta(25-35)induced neurotoxicity. In addition, tau protein hyperphosphorylation was found to increase after A beta exposure. All of these phenotypes induced by A beta(25-35) were markedly reversed by L-NBP. Pretreatment With L-NBP prior to A beta(25-35) exposure significantly elevated cell viability, and reduced A beta(25-35)-induced nuclear fragmentation and early apoptosis. Furthermore, immunoreactivity for hyperphosphorylation tau protein was significantly decreased by L-NBP treatment. Our results suggest that L-NBP may protect neurons against A beta-induced neurotoxicity via inhibiting tau protein hyperphosphorylation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.