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 Aβ intracerebroventricular infusion in rats. In the present study, we investigated the neuroprotective effects of l-NBP on beta-amyloid (Aβ)25–35-induced neuronal death/apoptosis and potential mechanisms in rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. Aβ25–35 significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that Aβ25–35-induced neurotoxicity. In addition, tau protein hyperphosphorylation was found to increase after Aβ exposure. All of these phenotypes induced by Aβ25–35 were markedly reversed by l-NBP. Pretreatment with l-NBP prior to Aβ25–35 exposure significantly elevated cell viability, and reduced Aβ25–35-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 Aβ-induced neurotoxicity via inhibiting tau protein hyperphosphorylation.