title: Anthoxanthin Polyphenols Attenuate Aβ Oligomer-induced Neuronal Responses Associated with Alzheimer's Disease.
abstract: OBJECTIVE
  Epidemiological evidence implicates polyphenols as potential natural therapeutics for Alzheimer's disease (AD). To investigate this prospect, five anthoxanthin polyphenols were characterized for their ability to reduce amyloid-β (Aβ) oligomer-induced neuronal responses by two mechanisms of action, modulation of oligomerization and antioxidant activity, as well as the synergy between these two mechanisms.
  
  
  METHODS
  Anthoxanthin oligomerization modulation and antioxidant capabilities were evaluated and correlated with anthoxanthin attenuation of oligomer-induced intracellular reactive oxygen species (ROS) and caspase activation using human neuroblastoma cell treatments designed to isolate these mechanisms of action and to achieve dual-action.
  
  
  RESULTS
  While modulation of oligomerization resulted in only minor reductions to neuronal responses, anthoxanthin antioxidant action significantly attenuated oligomer-induced intracellular ROS and caspase activation. Kaempferol uniquely exhibited synergism when the two mechanisms functioned in concert, leading to a pronounced reduction in both ROS and caspase activation.
  
  
  CONCLUSIONS
  Together, these findings identify the dominant mechanism by which these anthoxanthins attenuate Aβ oligomer-induced neuronal responses, elucidate their prospective synergy, and demonstrate the potential of anthoxanthin polyphenols as natural AD therapeutics.
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, SC, USA.
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Pate
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, SC, USA.
authors.forename: McCall
authors.initials: M
authors.lastname: Rogers
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, SC, USA.
authors.forename: John Will
authors.initials: JW
authors.lastname: Reed
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, SC, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: van der Munnik
authors.affiliation: Biomedical Engineering Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Steven Zebulon
authors.initials: SZ
authors.lastname: Vance
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, SC, USA.|Biomedical Engineering Program, University of South Carolina, Columbia, SC, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Moss
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D044949:Kaempferols; D047311:Luteolin / Q000494:pharmacology; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D044949:Kaempferols; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D059808:Polyphenols; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C006552:kaempferol; D047310:Apigenin; D006861:Hydrogen Peroxide; D020169:Caspases; D047311:Luteolin
keywords: Amyloid-β protein; Caspase activation; Oligomer; Polyphenol; Reactive oxygen species