摘要
Alzheimer＇s disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer＇s disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide （PT-3）, purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3 （125-200 nM） pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 （125-200 nM） inhibited scopolamine （2 mM）-induced generation of reactive oxygen species, cellular apoptosis, upregutation of ace- tylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer＇s disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this de- bilitating disease.
Alzheimer＇s disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer＇s disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide （PT-3）, purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3 （125-200 nM） pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 （125-200 nM） inhibited scopolamine （2 mM）-induced generation of reactive oxygen species, cellular apoptosis, upregutation of ace- tylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer＇s disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this de- bilitating disease.
基金
supported by a joint Mahidol University and The Thailand Research Fund(TRF)grant(IRG5780009)
TRF Royal Golden Jubilee Ph.D.Program(grant No.PHD/0175/2552)
the Office of the Higher Education Commission,Ministry of Education,Thailand
