ABSTRACT
AIMS: 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-ß (Aß) 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 Aß oligomer-induced neuronal responses, elucidate their prospective synergy, and demonstrate the potential of anthoxanthin polyphenols as natural AD therapeutics.
