L-3-n-Butylphthalide attenuates β-amyloid-induced toxicity in neuroblastoma SH-SY5Y cells through regulating mitochondrion-mediated apoptosis and MAPK signaling

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Amyloid-beta protein (A beta), the hallmark of AD, invokes a cascade of mitochondrial dysfunction and eventually leads to neuronal death. L-3-n-Butylphthalide (L-NBP) has shown the potent neuroprotective effects in stroke and AD animal models. The present study is to evaluate the neuroprotective effect of L-NBP on A beta(25-35)-induced neuronal injury and the possible mechanism in the human neuroblastoma SH-SY5Y cells. Our results showed that L-NBP significantly attenuated A beta(25-35)-induced cell death and reduced neuronal apoptosis. L-NBP significantly inhibited A beta(25-35)-induced mitochondrial dysfunction, including mitochondrial membrane potential reduction, and reactive oxygen species production. Furthermore, L-NBP could partially reverse the elevations of A beta(25-35)-induced active caspase-3, caspase-9, and cytochrome c expressions, and the downregulation of anti-apoptosis protein Bcl-2. Moreover, L-NBP markedly inhibited the activations of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway. These results demonstrated that L-NBP was capable of protecting neuronal cells from A beta(25-35)-induced toxicity through a mitochondrial-dependent apoptotic pathway. Thus, L-NBP shows promising candidate of multi-target neuronal protective agent for the treatment of AD.