Anthoxanthin Polyphenols Attenuate A Oligomer-induced Neuronal Responses Associated with Alzheimer's Disease

被引:32
作者
Pate, Kayla M. [1 ,3 ]
Rogers, McCall [1 ]
Reed, John Will [1 ,4 ]
van der Munnik, Nicholas [1 ]
Vance, Steven Zebulon [2 ]
Moss, Melissa A. [1 ,2 ]
机构
[1] Univ South Carolina, Dept Chem Engn, Columbia, SC USA
[2] Univ South Carolina, Biomed Engn Program, Columbia, SC USA
[3] Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA
[4] Home Depot, Data Analyt, Atlanta, GA 30318 USA
基金
美国国家卫生研究院;
关键词
Amyloid-beta protein; Caspase activation; Oligomer; Polyphenol; Reactive oxygen species; AMYLOID-BETA OLIGOMERS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; NATURAL POLYPHENOLS; FIBRIL FORMATION; NADPH OXIDASE; FLAVONOIDS; MECHANISMS; APOPTOSIS; PREVENTION;
D O I
10.1111/cns.12659
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
AimsEpidemiological 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- (A) oligomer-induced neuronal responses by two mechanisms of action, modulation of oligomerization and antioxidant activity, as well as the synergy between these two mechanisms. MethodsAnthoxanthin 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. ResultsWhile 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. ConclusionsTogether, these findings identify the dominant mechanism by which these anthoxanthins attenuate A oligomer-induced neuronal responses, elucidate their prospective synergy, and demonstrate the potential of anthoxanthin polyphenols as natural AD therapeutics.
引用
收藏
页码:135 / 144
页数:10
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