title: Protective effect of centipedegrass against Aβ oligomerization and Aβ-mediated cell death in PC12 cells.
abstract: BACKGROUND
  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.
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors: Institute of Agriculture and Life Science, College of Veterinary Medicine, Gyeongsang National University , Jinju , Korea .
authors: Yuno
authors: Y
authors: Song
authors: Hong-Duck
authors: HD
authors: Kim
authors: Min-Kwon
authors: MK
authors: Lee
authors: Mun Ki
authors: MK
authors: Kim
authors: Suk-Nam
authors: SN
authors: Kang
authors: Yeoung-Gyu
authors: YG
authors: Ko
authors: Chung-Kil
authors: CK
authors: Won
authors: Gon-Sup
authors: GS
authors: Kim
authors: Seung Sik
authors: SS
authors: Lee
authors: Hyoung-Woo
authors: HW
authors: Bai
authors: Byung Yeoup
authors: BY
authors: Chung
authors: Jae-Hyeon
authors: JH
authors: Cho
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D005960:Glucosides / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D006109:Poaceae / Q000737:chemistry; D066263:Protein Aggregation, Pathological; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005960:Glucosides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; C075222:amyloid beta-protein (1-42); C114429:maysin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer's disease; neurotoxicity; β-secretase