l-3-n-Butylphthalide ameliorates beta-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 Abeta intracerebroventricular infusion in rats. In the present study, we investigated the neuroprotective effects of l-NBP on beta-amyloid (Abeta)25-35-induced neuronal death/apoptosis and potential mechanisms in rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. Abeta25-35 significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that Abeta25-35-induced neurotoxicity. In addition, tau protein hyperphosphorylation was found to increase after Abeta exposure. All of these phenotypes induced by Abeta25-35 were markedly reversed by l-NBP. Pretreatment with l-NBP prior to Abeta25-35 exposure significantly elevated cell viability, and reduced Abeta25-35-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 Abeta-induced neurotoxicity via inhibiting tau protein hyperphosphorylation.
Peng
Ying
Y
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1, Xiannongtan Street, Xuanwu District, Beijing 100050, China.
Xing
Changhong
C
Lemere
Cynthia A
CA
Chen
Guiquan
G
Wang
Ling
L
Feng
Yipu
Y
Wang
Xiaoliang
X
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000077102:Apium; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D001572:Benzofurans; C518724:CML-1 plant extract; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35); C027125:3-n-butylphthalide