Targeting NRF2 for improved skin barrier function and photoprotection: Focus on the achiote-derived apocarotenoid bixin

Montserrat Rojo de la Vega, Andrea Krajisnik, Donna Zhang, Georg T Wondrak

Research output: Contribution to journalReview article

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1371
JournalNutrients
Volume9
Issue number12
DOIs
StatePublished - Dec 18 2017

Fingerprint

NF-E2-Related Factor 2
Bixa orellana
photostability
skin (animal)
Skin
antioxidants
Antioxidants
Conservation of Natural Resources
Phase II Metabolic Detoxication
Food Coloring Agents
food coloring
natural foods
keratinocytes
topical application
environmental protection
DNA repair
Peroxisome Proliferator-Activated Receptors
Toll-Like Receptor 4
tissue repair
anti-inflammatory activity

Keywords

  • Achiote
  • Bixin
  • NRF2
  • PPARα
  • Skin barrier function
  • Skin photodamage
  • Solar ultraviolet (UV)

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Targeting NRF2 for improved skin barrier function and photoprotection : Focus on the achiote-derived apocarotenoid bixin. / de la Vega, Montserrat Rojo; Krajisnik, Andrea; Zhang, Donna; Wondrak, Georg T.

In: Nutrients, Vol. 9, No. 12, 1371, 18.12.2017.

Research output: Contribution to journalReview article

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title = "Targeting NRF2 for improved skin barrier function and photoprotection: Focus on the achiote-derived apocarotenoid bixin",
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.",
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