Sesamol decreases melanin biosynthesis in melanocyte cells and zebrafish: Possible involvement of MITF via the intracellular cAMP and p38/JNK signalling pathways

Exp Dermatol. 2015 Oct;24(10):761-6. doi: 10.1111/exd.12765. Epub 2015 Jul 14.

Abstract

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasma, freckles, age spots and chloasma. The aim of this study was to investigate the antimelanogenic effect of sesamol, an active lignan isolated from Sesamum indicum, in melan-a cells. Sesamol strongly inhibited melanin biosynthesis and the activity of intracellular tyrosinase by decreasing cyclic adenosine monophosphate (cAMP) accumulation. Sesamol significantly decreased the expression of melanogenesis-related genes, such as tyrosinase, tyrosinase-related protein-1,2 (TRP-1,2), microphthalmia-associated transcription factor (MITF) and melanocortin 1 receptor (MC1R). In addition, sesamol also induces phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Moreover, sesamol dose-dependently decreased zebrafish pigment formation, tyrosinase activity and expression of melanogenesis-related genes. These findings indicate that sesamol inhibited melanin biosynthesis by down-regulating tyrosinase activity and melanin production via regulation of gene expression of melanogenesis-related proteins through modulation of MITF activity, which promoted phosphorylation of p38 and JNK in melan-a cells. Together, these results suggest that sesamol strongly inhibits melanin biosynthesis, and therefore, sesamol represents a new skin-whitening agent for use in cosmetics.

Keywords: antimelanogenic agents; cyclic adenosine monophosphate; microphthalmia-associated transcription factor; sesamol; tyrosinase; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Benzodioxoles / pharmacology*
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression / drug effects*
  • Intramolecular Oxidoreductases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Melanins / biosynthesis*
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Microphthalmia-Associated Transcription Factor / genetics
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / genetics
  • Phenols / pharmacology*
  • Phosphorylation / drug effects
  • Pigmentation / drug effects
  • Protein Biosynthesis / drug effects*
  • Receptor, Melanocortin, Type 1 / genetics
  • Zebrafish
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Benzodioxoles
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Phenols
  • Receptor, Melanocortin, Type 1
  • sesamol
  • Cyclic AMP
  • Oxidoreductases
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase