Protective effect of centipedegrass against A beta oligomerization and A beta-mediated cell death in PC12 cells

Context: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal accumulation of beta-amyloid (A beta). Multiple A beta-aggregated species have been identified, and neurotoxicity appears to be correlated with the amount of non-fibrillar oligomers. Potent inhibitors of A beta oligomer formation or A beta-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 A beta aggregation, BACE1 activity, and toxicity at neuronal cell. Materials and methods: The inhibitory effect of CG extracts toward aggregation of A beta 42 was investigated in the absence and presence of 50 mu g/mL CG. We investigated the inhibitory effects of CG (0-5 mu g/mL) on BACE1 using fluorescence resonance energy transfer (FRET)-based assay. The effects of CG (0-75 mu g/mL) on A beta 42-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 A beta oligomeric forms such as the monomer, dimer, trimer, and highly aggregated oligomeric forms were remarkably inhibited in the presence of 50 mu g/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 mg/mL, respectively. Moreover, the neurotoxicity induced by A beta 42 was significantly reduced by treatment of EA-CG, and the 75 mu g/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 A beta formation and reducing BACE1 activity. Maysin in CG could be an excellent therapeutic candidate for the prevention of AD.