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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Targeting NRF2 for Improved Skin Barrier Function and Photoprotection: Focus on the Achiote-Derived Apocarotenoid Bixin.

Authors: Rojo de la Vega, Montserrat; Krajisnik, Andrea; Zhang, Donna D; Wondrak, Georg T

Published In Nutrients, (2017 Dec 18)

Abstract: The transcription factor NRF2 (nuclear factor-E2-related factor 2) orchestrates major cellular defense mechanisms including phase-II detoxification, inflammatory signaling, DNA repair, and antioxidant response. Recent studies strongly suggest a protective role of NRF2-mediated gene expression in the suppression of cutaneous photodamage induced by solar UV (ultraviolet) radiation. The apocarotenoid bixin, a Food and Drug Administration (FDA)-approved natural food colorant (referred to as 'annatto') originates from the seeds of the achiote tree native to tropical America, consumed by humans since ancient times. Use of achiote preparations for skin protection against environmental insult and for enhanced wound healing has long been documented. We have recently reported that (i) bixin is a potent canonical activator of the NRF2-dependent cytoprotective response in human skin keratinocytes; that (ii) systemic administration of bixin activates NRF2 with protective effects against solar UV-induced skin damage; and that (iii) bixin-induced suppression of photodamage is observable in Nrf2+/+ but not in Nrf2-/- SKH-1 mice confirming the NRF2-dependence of bixin-induced antioxidant and anti-inflammatory effects. In addition, bixin displays molecular activities as sacrificial antioxidant, excited state quencher, PPAR (peroxisome proliferator-activated receptor) α/γ agonist, and TLR (Toll-like receptor) 4/NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) antagonist, all of which might be relevant to the enhancement of skin barrier function and environmental stress protection. Potential skin photoprotection and photochemoprevention benefits provided by topical application or dietary consumption of this ethno-pharmacologically validated phytochemical originating from the Americas deserves further preclinical and clinical examination.

PubMed ID: 29258247 Exiting the NIEHS site

MeSH Terms: Animals; Antioxidants/pharmacology; Bixaceae; Carotenoids/pharmacology*; DNA Repair; Disease Models, Animal; Humans; Keratinocytes/drug effects; Keratinocytes/metabolism; Keratinocytes/radiation effects; Mice; NF-E2-Related Factor 2/genetics; NF-E2-Related Factor 2/metabolism*; NF-kappa B/genetics; NF-kappa B/metabolism; Oxidative Stress/drug effects; PPAR alpha/genetics; PPAR alpha/metabolism; PPAR gamma/genetics; PPAR gamma/metabolism; Plant Extracts/pharmacology*; Skin Neoplasms/drug therapy; Skin Neoplasms/etiology; Skin/cytology; Skin/drug effects*; Skin/metabolism; Skin/radiation effects; Sunlight; Toll-Like Receptor 4/genetics; Toll-Like Receptor 4/metabolism; Ultraviolet Rays/adverse effects

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