Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin
AffiliationUniv Arizona, Coll Pharm, Dept Pharmacol & Toxicol
MetadataShow full item record
PublisherFRONTIERS MEDIA SA
CitationRojo de la Vega M, Zhang DD and Wondrak GT (2018) Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin. Front. Pharmacol. 9:287. doi: 10.3389/fphar.2018.00287
JournalFRONTIERS IN PHARMACOLOGY
Rights© 2018 Rojo de la Vega, Zhang and Wondrak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractEnvironmental 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.
VersionFinal published version
SponsorsNational Institutes of Health [R03 CA212719, R03 CA167580, R01 ES026845]; University of Arizona Cancer Center Support Grant; NIH [CA023074, ES007091, ES006694]
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