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Nrf2-mediated therapeutic effects of dietary flavones in different diseases

Oxidative stress (OS) is a pathological status that occurs when the body’s balance between oxidants and antioxidant defense systems is broken, which can promote the development of many diseases. Nrf2, a redox-sensitive transcription encoded by NFE2L2, is the master regulator of phase II antioxidant...

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Autores principales: Huang, Wenkai, Zhong, Yuan, Gao, Botao, Zheng, Bowen, Liu, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520786/
https://www.ncbi.nlm.nih.gov/pubmed/37767395
http://dx.doi.org/10.3389/fphar.2023.1240433
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author Huang, Wenkai
Zhong, Yuan
Gao, Botao
Zheng, Bowen
Liu, Yi
author_facet Huang, Wenkai
Zhong, Yuan
Gao, Botao
Zheng, Bowen
Liu, Yi
author_sort Huang, Wenkai
collection PubMed
description Oxidative stress (OS) is a pathological status that occurs when the body’s balance between oxidants and antioxidant defense systems is broken, which can promote the development of many diseases. Nrf2, a redox-sensitive transcription encoded by NFE2L2, is the master regulator of phase II antioxidant enzymes and cytoprotective genes. In this context, Nrf2/ARE signaling can be a compelling target against OS-induced diseases. Recently, natural Nrf2/ARE regulators like dietary flavones have shown therapeutic potential in various acute and chronic diseases such as diabetes, neurodegenerative diseases, ischemia-reperfusion injury, and cancer. In this review, we aim to summarize nrf2-mediated protective effects of flavones in different conditions. Firstly, we retrospected the mechanisms of how flavones regulate the Nrf2/ARE pathway and introduced the mediator role Nrf2 plays in inflammation and apoptosis. Then we review the evidence that flavones modulated Nrf2/ARE pathway to prevent diseases in experimental models. Based on these literature, we found that flavones could regulate Nrf2 expression by mechanisms below: 1) dissociating the binding between Nrf2 and Keap1 via PKC-mediated Nrf2 phosphorylation and P62-mediated Keap1 autophagic degradation; 2) regulating Nrf2 nuclear translocation by various kinases like AMPK, MAPKs, Fyn; 3) decreasing Nrf2 ubiquitination and degradation via activating sirt1 and PI3K/AKT-mediated GSK3 inhibition; and 4) epigenetic alternation of Nrf2 such as demethylation at the promoter region and histone acetylation. In conclusion, flavones targeting Nrf2 can be promising therapeutic agents for various OS-related disorders. However, there is a lack of investigations on human subjects, and new drug delivery systems to improve flavones’ treatment efficiency still need to be developed.
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spelling pubmed-105207862023-09-27 Nrf2-mediated therapeutic effects of dietary flavones in different diseases Huang, Wenkai Zhong, Yuan Gao, Botao Zheng, Bowen Liu, Yi Front Pharmacol Pharmacology Oxidative stress (OS) is a pathological status that occurs when the body’s balance between oxidants and antioxidant defense systems is broken, which can promote the development of many diseases. Nrf2, a redox-sensitive transcription encoded by NFE2L2, is the master regulator of phase II antioxidant enzymes and cytoprotective genes. In this context, Nrf2/ARE signaling can be a compelling target against OS-induced diseases. Recently, natural Nrf2/ARE regulators like dietary flavones have shown therapeutic potential in various acute and chronic diseases such as diabetes, neurodegenerative diseases, ischemia-reperfusion injury, and cancer. In this review, we aim to summarize nrf2-mediated protective effects of flavones in different conditions. Firstly, we retrospected the mechanisms of how flavones regulate the Nrf2/ARE pathway and introduced the mediator role Nrf2 plays in inflammation and apoptosis. Then we review the evidence that flavones modulated Nrf2/ARE pathway to prevent diseases in experimental models. Based on these literature, we found that flavones could regulate Nrf2 expression by mechanisms below: 1) dissociating the binding between Nrf2 and Keap1 via PKC-mediated Nrf2 phosphorylation and P62-mediated Keap1 autophagic degradation; 2) regulating Nrf2 nuclear translocation by various kinases like AMPK, MAPKs, Fyn; 3) decreasing Nrf2 ubiquitination and degradation via activating sirt1 and PI3K/AKT-mediated GSK3 inhibition; and 4) epigenetic alternation of Nrf2 such as demethylation at the promoter region and histone acetylation. In conclusion, flavones targeting Nrf2 can be promising therapeutic agents for various OS-related disorders. However, there is a lack of investigations on human subjects, and new drug delivery systems to improve flavones’ treatment efficiency still need to be developed. Frontiers Media S.A. 2023-09-12 /pmc/articles/PMC10520786/ /pubmed/37767395 http://dx.doi.org/10.3389/fphar.2023.1240433 Text en Copyright © 2023 Huang, Zhong, Gao, Zheng and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Huang, Wenkai
Zhong, Yuan
Gao, Botao
Zheng, Bowen
Liu, Yi
Nrf2-mediated therapeutic effects of dietary flavones in different diseases
title Nrf2-mediated therapeutic effects of dietary flavones in different diseases
title_full Nrf2-mediated therapeutic effects of dietary flavones in different diseases
title_fullStr Nrf2-mediated therapeutic effects of dietary flavones in different diseases
title_full_unstemmed Nrf2-mediated therapeutic effects of dietary flavones in different diseases
title_short Nrf2-mediated therapeutic effects of dietary flavones in different diseases
title_sort nrf2-mediated therapeutic effects of dietary flavones in different diseases
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520786/
https://www.ncbi.nlm.nih.gov/pubmed/37767395
http://dx.doi.org/10.3389/fphar.2023.1240433
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