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Front. Pharmacol. | doi: 10.3389/fphar.2018.00287

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

  • 1Pharmacology and Toxicology, College of Pharmacy, University of Arizona, United States

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 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 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.

Keywords: Nrf2, Bixin, UV, PUVA, skin oxidative stress, photodamage, Sunburn, Hair graying

Received: 01 Feb 2018; Accepted: 13 Mar 2018.

Edited by:

Andrzej T. Slominski, University of Tennessee Health Science Center, United States

Reviewed by:

Jean Christopher Chamcheu, University of Louisiana at Monroe, United States
Thomas Haarmann-Stemmann, Leibniz-Institut für umweltmedizinische Forschung (IUF), Germany  

Copyright: © 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). 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.

* Correspondence:
Dr. Donna D. Zhang, College of Pharmacy, University of Arizona, Pharmacology and Toxicology, UA Cancer Center, 1515 N. Campbell Ave, Tucson, 85724, AZ, United States,
Dr. Georg T. Wondrak, College of Pharmacy, University of Arizona, Pharmacology and Toxicology, UA Cancer Center, 1515 N. Campbell Ave, Tucson, 85724, AZ, United States,