β-Cryptoxanthin suppresses UVB-induced melanogenesis in mouse: involvement of the inhibition of prostaglandin E2 and melanocyte-stimulating hormone pathways

J Pharm Pharmacol. 2012 Aug;64(8):1165-76. doi: 10.1111/j.2042-7158.2012.01495.x. Epub 2012 Mar 27.

Abstract

Objective: β-cryptoxanthin (β-CPX) is a carotenoid that is widely contained in the fruits of citrus plants. We evaluated the effect of β-CPX on UVB-induced pigmentation and mRNA expression related to melanogenesis in mouse skin. In addition, changes in melanogenic molecules were evaluated in cultured melanocytes stimulated with prostaglandin (PG) E(2), melanocyte-stimulating hormone (MSH) and endothelin (ET)-1.

Methods: Mice were irradiated with UVB and were given β-CPX (0.1, 1 and 10 mg/kg) orally for 14 days. Pigmentation was evaluated by skin colour change and microscopic observation. Total RNA was obtained from the skin and the expression of melanogenic mRNA was evaluated by RT-PCR. In cell culture studies, human melanocytes were cultured with β-CPX and melanogenic stimulants (PGE(2), MSH and ET-1) for 6-10 days. Melanin contents, dendricity, melanogenic mRNA and phosphorylation of cyclic AMP response element-binding protein (CREB) were evaluated.

Key findings: β-CPX (10 mg/kg) significantly suppressed skin pigmentation and mRNA expression of cyclooxygenase-2, ET-1 receptors, low-affinity neurotrophin receptor, PGE(2) receptor (EP1), melanocortin 1 receptor (MC1R), tyrosinase (Tyr), tyrosinase-related protein (Tyrp) 1 and microphthalmia transcription factor. β-CPX (10 µg/ml) suppressed melanogenesis induced by PGE(2), MSH and ET-1. In the PGE(2)-stimulated melanocytes, mRNA expressions of EP-1, Tyr and Tyrp1 and phosphorylation of CREB protein were suppressed. In the ET-1-stimulated cells, only expression of CREB protein was suppressed. In the MSH-induced cells, mRNA expression of MC1R and Tyrp1 and protein expression of CREB were suppressed.

Conclusion: Oral administration of β-CPX was found to suppress UVB-induced melanogenesis. Suppression of melanogenic enzymes, receptors of melanogenic stimulators, expression and phosphorylation of CREB are thought to be involved in the mechanism.

MeSH terms

  • Animals
  • Citrus / chemistry*
  • Cryptoxanthins
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / antagonists & inhibitors*
  • Dinoprostone / pharmacology
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Endothelin-1 / pharmacology
  • Fruit
  • Humans
  • Male
  • Melanins / biosynthesis*
  • Melanocyte-Stimulating Hormones / antagonists & inhibitors*
  • Melanocyte-Stimulating Hormones / pharmacology
  • Melanocytes / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Hairless
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • RNA, Messenger / metabolism
  • Receptor, Endothelin A / metabolism
  • Receptors, Corticotropin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / drug effects
  • Skin / metabolism
  • Skin / radiation effects
  • Skin Pigmentation / drug effects*
  • Skin Pigmentation / radiation effects
  • Ultraviolet Rays
  • Xanthophylls / pharmacology
  • Xanthophylls / therapeutic use*

Substances

  • Cryptoxanthins
  • Cyclic AMP Response Element-Binding Protein
  • Endothelin-1
  • Melanins
  • Membrane Glycoproteins
  • Microphthalmia-Associated Transcription Factor
  • Plant Extracts
  • RNA, Messenger
  • Receptor, Endothelin A
  • Receptors, Corticotropin
  • Xanthophylls
  • Melanocyte-Stimulating Hormones
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • Monophenol Monooxygenase
  • Cyclooxygenase 2
  • Dinoprostone