Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives
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 amy...
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doaj-9486b2032bc34a828370331c915a724f2021-09-25T23:38:22ZengMDPI AGAntioxidants2076-39212021-09-01101428142810.3390/antiox10091428Autoxidation Enhances Anti-Amyloid Potential of Flavone DerivativesAndrius Sakalauskas0Mantas Ziaunys1Ruta Snieckute2Vytautas Smirnovas3Life Sciences Center, Institute of Biotechnology, Vilnius University, LT-10257 Vilnius, LithuaniaLife Sciences Center, Institute of Biotechnology, Vilnius University, LT-10257 Vilnius, LithuaniaLife Sciences Center, Institute of Biotechnology, Vilnius University, LT-10257 Vilnius, LithuaniaLife Sciences Center, Institute of Biotechnology, Vilnius University, LT-10257 Vilnius, LithuaniaThe 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.https://www.mdpi.com/2076-3921/10/9/1428aggregationamyloid-betainsulinflavonesinhibitionautoxidation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrius Sakalauskas Mantas Ziaunys Ruta Snieckute Vytautas Smirnovas |
spellingShingle |
Andrius Sakalauskas Mantas Ziaunys Ruta Snieckute Vytautas Smirnovas Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives Antioxidants aggregation amyloid-beta insulin flavones inhibition autoxidation |
author_facet |
Andrius Sakalauskas Mantas Ziaunys Ruta Snieckute Vytautas Smirnovas |
author_sort |
Andrius Sakalauskas |
title |
Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title_short |
Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title_full |
Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title_fullStr |
Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title_full_unstemmed |
Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title_sort |
autoxidation enhances anti-amyloid potential of flavone derivatives |
publisher |
MDPI AG |
series |
Antioxidants |
issn |
2076-3921 |
publishDate |
2021-09-01 |
description |
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. |
topic |
aggregation amyloid-beta insulin flavones inhibition autoxidation |
url |
https://www.mdpi.com/2076-3921/10/9/1428 |
work_keys_str_mv |
AT andriussakalauskas autoxidationenhancesantiamyloidpotentialofflavonederivatives AT mantasziaunys autoxidationenhancesantiamyloidpotentialofflavonederivatives AT rutasnieckute autoxidationenhancesantiamyloidpotentialofflavonederivatives AT vytautassmirnovas autoxidationenhancesantiamyloidpotentialofflavonederivatives |
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