title: Osthole reverses beta-amyloid peptide cytotoxicity on neural cells by enhancing cyclic AMP response element-binding protein phosphorylation.
abstract: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Qingping
authors.initials: Q
authors.lastname: Wen
authors.forename: Wenbo
authors.initials: W
authors.lastname: Liang
authors.forename: Tingguo
authors.initials: T
authors.lastname: Kang
authors.forename: Lu
authors.initials: L
authors.lastname: Ren
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Jingxian
authors.initials: J
authors.lastname: Yang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016704:Synapsins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; C494826:BAX protein, human; C115163:CREB1 protein, human; D003374:Coumarins; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D016704:Synapsins; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C046627:osthol