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Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin

Environmental exposure to solar ultraviolet (UV) radiation causes acute photodamage, premature aging, and skin cancer, attributable to UV-induced genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2 [nuclear factor erythroid 2 (E2)-related factor 2] is the master regulator of...

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Autores principales: Rojo de la Vega, Montserrat, Zhang, Donna D., Wondrak, Georg T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880955/
https://www.ncbi.nlm.nih.gov/pubmed/29636694
http://dx.doi.org/10.3389/fphar.2018.00287
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author Rojo de la Vega, Montserrat
Zhang, Donna D.
Wondrak, Georg T.
author_facet Rojo de la Vega, Montserrat
Zhang, Donna D.
Wondrak, Georg T.
author_sort Rojo de la Vega, Montserrat
collection PubMed
description Environmental exposure to solar ultraviolet (UV) radiation causes acute photodamage, premature aging, and skin cancer, attributable to UV-induced genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2 [nuclear factor erythroid 2 (E2)-related factor 2] is the master regulator of the cellular antioxidant response protecting skin against various environmental stressors including UV radiation and electrophilic pollutants. NRF2 in epidermal keratinocytes can be activated using natural chemopreventive compounds such as the apocarotenoid bixin, an FDA-approved food additive and cosmetic ingredient from the seeds of the achiote tree (Bixa orellana). Here, we tested the feasibility of topical use of bixin for NRF2-dependent skin photoprotection in two genetically modified mouse models [SKH1 and C57BL/6J (Nrf2(+/+) versus Nrf2(-/-))]. First, we observed that a bixin formulation optimized for topical NRF2 activation suppresses acute UV-induced photodamage in Nrf2(+/+) but not Nrf2(-/-) SKH1 mice, a photoprotective effect indicated by reduced epidermal hyperproliferation and oxidative DNA damage. Secondly, it was demonstrated that topical bixin suppresses PUVA (psoralen + UVA)-induced hair graying in Nrf2(+/+) but not Nrf2(-/-) C57BL/6J mice. Collectively, this research provides the first in vivo evidence that topical application of bixin can protect against UV-induced photodamage and PUVA-induced loss of hair pigmentation through NRF2 activation. Topical NRF2 activation using bixin may represent a novel strategy for human skin photoprotection, potentially complementing conventional sunscreen-based approaches.
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spelling pubmed-58809552018-04-10 Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin Rojo de la Vega, Montserrat Zhang, Donna D. Wondrak, Georg T. Front Pharmacol Pharmacology Environmental exposure to solar ultraviolet (UV) radiation causes acute photodamage, premature aging, and skin cancer, attributable to UV-induced genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2 [nuclear factor erythroid 2 (E2)-related factor 2] is the master regulator of the cellular antioxidant response protecting skin against various environmental stressors including UV radiation and electrophilic pollutants. NRF2 in epidermal keratinocytes can be activated using natural chemopreventive compounds such as the apocarotenoid bixin, an FDA-approved food additive and cosmetic ingredient from the seeds of the achiote tree (Bixa orellana). Here, we tested the feasibility of topical use of bixin for NRF2-dependent skin photoprotection in two genetically modified mouse models [SKH1 and C57BL/6J (Nrf2(+/+) versus Nrf2(-/-))]. First, we observed that a bixin formulation optimized for topical NRF2 activation suppresses acute UV-induced photodamage in Nrf2(+/+) but not Nrf2(-/-) SKH1 mice, a photoprotective effect indicated by reduced epidermal hyperproliferation and oxidative DNA damage. Secondly, it was demonstrated that topical bixin suppresses PUVA (psoralen + UVA)-induced hair graying in Nrf2(+/+) but not Nrf2(-/-) C57BL/6J mice. Collectively, this research provides the first in vivo evidence that topical application of bixin can protect against UV-induced photodamage and PUVA-induced loss of hair pigmentation through NRF2 activation. Topical NRF2 activation using bixin may represent a novel strategy for human skin photoprotection, potentially complementing conventional sunscreen-based approaches. Frontiers Media S.A. 2018-03-27 /pmc/articles/PMC5880955/ /pubmed/29636694 http://dx.doi.org/10.3389/fphar.2018.00287 Text en Copyright © 2018 Rojo de la Vega, Zhang and Wondrak. http://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 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
Rojo de la Vega, Montserrat
Zhang, Donna D.
Wondrak, Georg T.
Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
title Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
title_full Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
title_fullStr Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
title_full_unstemmed Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
title_short Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
title_sort topical bixin confers nrf2-dependent protection against photodamage and hair graying in mouse skin
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880955/
https://www.ncbi.nlm.nih.gov/pubmed/29636694
http://dx.doi.org/10.3389/fphar.2018.00287
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