title: β-Cryptoxanthin suppresses UVB-induced melanogenesis in mouse: involvement of the inhibition of prostaglandin E2 and melanocyte-stimulating hormone pathways.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Research & Development Division, Oryza Oil & Fat Chemical Co, Ltd, Ichinomiya, Ichinomiya, Aichi, Japan. kaihatsu@mri.biglobe.ne.jp
authors: Hiroshi
authors: H
authors: Shimoda
authors: Shao-Jie
authors: SJ
authors: Shan
authors: Junji
authors: J
authors: Tanaka
authors: Takashi
authors: T
authors: Maoka
mesh_terms: D000818:Animals; D002957:Citrus / Q000737:chemistry*; D065366:Cryptoxanthins; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005638:Fruit; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D009074:Melanocyte-Stimulating Hormones / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008544:Melanocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays; D024341:Xanthophylls / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D065366:Cryptoxanthins; D017362:Cyclic AMP Response Element-Binding Protein; D019332:Endothelin-1; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D010936:Plant Extracts; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D018043:Receptors, Corticotropin; D024341:Xanthophylls; D009074:Melanocyte-Stimulating Hormones; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D051546:Cyclooxygenase 2; D015232:Dinoprostone