Anthoxanthin Polyphenols Attenuate Aβ Oligomer‐induced Neuronal Responses Associated with Alzheimer's Disease

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‐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.