Protective effect of centipedegrass against Aß oligomerization and Aß-mediated cell death in PC12 cells.
Pharm Biol
; 53(9): 1260-6, 2015.
Article
em En
| MEDLINE
| ID: mdl-25853960
ABSTRACT
CONTEXT Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal accumulation of ß-amyloid (Aß). Multiple Aß-aggregated species have been identified, and neurotoxicity appears to be correlated with the amount of non-fibrillar oligomers. Potent inhibitors of Aß oligomer formation or Aß-induced cell toxicity have emerged as attractive means of therapeutic intervention. Eremochloa ophiuroide Hack. (Poaceae), also known as centipedegrass (CG), originates from China and South America and is reported to contain several C-glycosyl flavones and phenolic constituents. OBJECTIVE:
We investigated whether CG could suppress Aß aggregation, BACE1 activity, and toxicity at neuronal cell. MATERIALS ANDMETHODS:
The inhibitory effect of CG extracts toward aggregation of Aß42 was investigated in the absence and presence of 50 µg/mL CG. We investigated the inhibitory effects of CG (0-5 µg/mL) on BACE1 using fluorescence resonance energy transfer (FRET)-based assay. The effects of CG (0-75 µg/mL) on Aß42-induced neurotoxicity were examined in PC12 cells in the presence or absence of maysin and its derivatives of CG.RESULTS:
We isolated EA-CG fraction (70% MeOH fraction from EtOAc extracts) from methanol extracts of CG, which contained approximately 60% maysin and its derivatives. In the present studies, we found that several Aß oligomeric forms such as the monomer, dimer, trimer, and highly aggregated oligomeric forms were remarkably inhibited in the presence of 50 µg/mL of EA-CG. EA-CG also inhibited BACE1 enzyme activity in a dose-dependent manner. EA-CG treatment generated approximately 50% or 85% inhibition to the control at the tested concentrations of 1 or 5 µg/mL, respectively. Moreover, the neurotoxicity induced by Aß42 was significantly reduced by treatment of EA-CG, and the 75 µg/mL EA-CG treatment significantly increased cell viability up to 82.5%. DISCUSSION ANDCONCLUSION:
These results suggested that the anti-Alzheimer's effects of CG occurred through inhibition of neuronal cell death by intervening with oligomeric Aß formation and reducing BACE1 activity. Maysin in CG could be an excellent therapeutic candidate for the prevention of AD.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
/
Plantas_medicinales
Assunto principal:
Fragmentos de Peptídeos
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Extratos Vegetais
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Peptídeos beta-Amiloides
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Ácido Aspártico Endopeptidases
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Fármacos Neuroprotetores
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Inibidores Enzimáticos
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Secretases da Proteína Precursora do Amiloide
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Poaceae
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Neurônios
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2015
Tipo de documento:
Article