Osthole Reverses Beta-Amyloid Peptide Cytotoxicity on Neural Cells by Enhancing Cyclic AMP Response Element-Binding Protein Phosphorylation
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概要
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Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). Previous studies have demonstrated the neuroprotective role of osthole against oxygen and glucose deprivation in cortical neurons. However, the effects of osthole on Aβ-induced neurotoxicity in neural cells have rarely been reported. The current study was designed to investigate the protective effects of osthole on a cell model of AD insulted by exogenous Aβ25-35 and the potential mechanism(s). In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence analysis, apoptosis assay, reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) techniques were used in primary cortical neurons and SH-SY5Y cells. Our data showed that osthole reduced intracellular Aβ levels in neural cells, which was associated with decreased BACE1 protein; osthole reversed exogenous Aβ25-35-induced cell viability loss, apoptosis, and synapsin-1 reduction, which was related to the reestablishment of phosphorylation of cyclic AMP response element-binding protein (CREB). The collective evidence indicates that osthole possesses the ability to protect cortical neurons and SH-SY5Y cells against Aβ injury, and the underlying mechanism may be attributed to the enhancement of CREB phosphorylation.
著者
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Zhao Dan
School Of Information Science Japan Advanced Institute Of Science And Technology
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Hu Yu
School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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Wen Qingping
First Affiliated Hospital, Dalian Medical University
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Liang Wenbo
School of Medicine, Dalian University
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Kang Tingguo
School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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Ren Lu
School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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Zhang Nan
School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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Sun Dong
School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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Yang Jingxian
School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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ZHAO Dan
School of Computer, National University of Defense Technology
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- Osthole Reverses Beta-Amyloid Peptide Cytotoxicity on Neural Cells by Enhancing Cyclic AMP Response Element-Binding Protein Phosphorylation