Journal
ANTIOXIDANTS
Volume 10, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/antiox10091428
Keywords
aggregation; amyloid-beta; insulin; flavones; inhibition; autoxidation
Funding
- Research Council of Lithuania [S-SEN-20-3]
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Flavones, a group of natural antioxidants, have been shown to impact the aggregation process of amyloidogenic proteins and peptides, with oxidized flavones demonstrating even greater potency in inhibiting aggregation. The position of hydroxyl groups on flavones plays a role in their autoxidation tendency and effectiveness as inhibitors against amyloid aggregation, showing potential for therapeutic applications.
The increasing prevalence of amyloid-related disorders, such as Alzheimer's or Parkinson's disease, raises the need for effective anti-amyloid drugs. It has been shown on numerous occasions that flavones, a group of naturally occurring anti-oxidants, can impact the aggregation process of several amyloidogenic proteins and peptides, including amyloid-beta. Due to flavone autoxidation at neutral pH, it is uncertain if the effective inhibitor is the initial molecule or a product of this reaction, as many anti-amyloid assays attempt to mimic physiological conditions. In this work, we examine the aggregation-inhibiting properties of flavones before and after they are oxidized. The oxidation of flavones was monitored by measuring the UV-vis absorbance spectrum change over time. The protein aggregation kinetics were followed by measuring the amyloidophilic dye thioflavin-T (ThT) fluorescence intensity change. Atomic force microscopy was employed to image the aggregates formed with the most prominent inhibitors. We demonstrate that flavones, which undergo autoxidation, have a far greater potency at inhibiting the aggregation of both the disease-related amyloid-beta, as well as a model amyloidogenic protein-insulin. Oxidized 6,2 ',3 '-trihydroxyflavone was the most potent inhibitor affecting both insulin (7-fold inhibition) and amyloid-beta (2-fold inhibition). We also show that this tendency to autoxidize is related to the positions of the flavone hydroxyl groups.
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