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

Lei, Hui; Zhao, Chun-Yang; Liu, Dong-Mei; Zhang, Yu; Li, Lin; Wang, Xiao-Liang; Peng, Ying

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Amyloid-β protein (Aβ), 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 Aβ25–35-induced neuronal injury and the possible mechanism in the human neuroblastoma SH-SY5Y cells. Our results showed that l-NBP significantly attenuated Aβ25–35-induced cell death and reduced neuronal apoptosis. l-NBP significantly inhibited Aβ25–35-induced mitochondrial dysfunction, including mitochondrial membrane potential reduction, and reactive oxygen species production. Furthermore, l-NBP could partially reverse the elevations of Aβ25–35-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 Aβ25–35-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.

ALZHEIMER'S disease; ANALYSIS of variance; APOPTOSIS; BIOLOGICAL assay; CELL culture; CELLULAR signal transduction; HETEROCYCLIC compounds; MITOCHONDRIA; MOLECULAR structure; NEURONS; PROTEIN kinases; PROTEINS; RESEARCH funding; WESTERN immunoblotting; PLANT extracts; DATA analysis software; DESCRIPTIVE statistics

Journal of Asian Natural Products Research, 2014, Vol 16, Issue 8, p854

1028-6020

Academic Journal

10.1080/10286020.2014.939586