Cargando…
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...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465893/ https://www.ncbi.nlm.nih.gov/pubmed/34573060 http://dx.doi.org/10.3390/antiox10091428 |
_version_ | 1784572992693469184 |
---|---|
author | Sakalauskas, Andrius Ziaunys, Mantas Snieckute, Ruta Smirnovas, Vytautas |
author_facet | Sakalauskas, Andrius Ziaunys, Mantas Snieckute, Ruta Smirnovas, Vytautas |
author_sort | Sakalauskas, Andrius |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8465893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84658932021-09-27 Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives Sakalauskas, Andrius Ziaunys, Mantas Snieckute, Ruta Smirnovas, Vytautas Antioxidants (Basel) Article 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. MDPI 2021-09-07 /pmc/articles/PMC8465893/ /pubmed/34573060 http://dx.doi.org/10.3390/antiox10091428 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sakalauskas, Andrius Ziaunys, Mantas Snieckute, Ruta Smirnovas, Vytautas Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title | 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_short | Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives |
title_sort | autoxidation enhances anti-amyloid potential of flavone derivatives |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465893/ https://www.ncbi.nlm.nih.gov/pubmed/34573060 http://dx.doi.org/10.3390/antiox10091428 |
work_keys_str_mv | AT sakalauskasandrius autoxidationenhancesantiamyloidpotentialofflavonederivatives AT ziaunysmantas autoxidationenhancesantiamyloidpotentialofflavonederivatives AT snieckuteruta autoxidationenhancesantiamyloidpotentialofflavonederivatives AT smirnovasvytautas autoxidationenhancesantiamyloidpotentialofflavonederivatives |