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Protective effect of centipedegrass against Aβ oligomerization and Aβ-mediated cell death in PC12 cells.

Abstract：

CONTEXT:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal accumulation of β-amyloid (Aβ). Multiple Aβ-aggregated species have been identified, and neurotoxicity appears to be correlated with the amount of non-fibrillar oligomers. Potent inhibitors of Aβ oligomer formation or Aβ-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 Aβ aggregation, BACE1 activity, and toxicity at neuronal cell. MATERIALS AND METHODS:The inhibitory effect of CG extracts toward aggregation of Aβ42 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 Aβ42-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 Aβ 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 Aβ42 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 AND CONCLUSION:These results suggested that the anti-Alzheimer's effects of CG occurred through inhibition of neuronal cell death by intervening with oligomeric Aβ formation and reducing BACE1 activity. Maysin in CG could be an excellent therapeutic candidate for the prevention of AD.

journal_name

Pharm Biol

journal_title

Pharmaceutical biology

authors

Song Y,Kim HD,Lee MK,Kim MK,Kang SN,Ko YG,Won CK,Kim GS,Lee SS,Bai HW,Chung BY,Cho JH

doi

10.3109/13880209.2014.974062

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

1260-6

issue

eissn

1388-0209

issn

1744-5116

journal_volume

pub_type

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Protective effect of centipedegrass against Aβ oligomerization and Aβ-mediated cell death in PC12 cells.