Dioscin Derived from Solanum melongena L. "Usukawamarunasu" Attenuates α-MSH-Induced Melanogenesis in B16 Murine Melanoma Cells via Downregulation of Phospho-CREB and MITF

J Food Sci. 2015 Oct;80(10):H2354-9. doi: 10.1111/1750-3841.13068. Epub 2015 Sep 9.

Abstract

This study aimed to chemically isolate and explore an antimelanogenesis inducer in extracts of Solanum melongena L. "Usukawamarunasu" eggplant. We successfully identified dioscin ([25R]-Spirost-5-en-3β-yl) 2-O-(6-deoxy-α-L-mannopyranosyl) - 4-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside] in the plant, and examined the effects of α-melanocyte-stimulating hormone (MSH)-induced melanogenesis in B16 murine melanoma cells by this plant-derived dioscin. Immunoblot analysis suggested that dioscin reduced the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2, resulting in inhibition of intracellular production of melanin. In addition, dioscin caused reduction of phosphorylated cAMP-responsive element binding protein 1 transcription factors (CREB), which led to a reduction of microphthalmia-related transcription factor (MITF) in α-MSH-stimulated cells, but did not affect phosphorylation of extracellular signal-regulated kinase. Furthermore, dioscin significantly downregulated the expression of tyrosinase, TRP-1, and TRP-2, which led to the reduction of α-MSH-induced melanogenesis in B16 cells. These results suggest that dioscin may decrease the level of MITF via inhibition of phosphorylation of CREB in α-MSH-induced melanogenesis in B16 cells.

Keywords: Solanum melongena L; cAMP-responsive element binding protein 1 transcription factors; dioscin; melanogenesis; microphthalmia-related transcription factor.

MeSH terms

  • Animals
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Diosgenin / analogs & derivatives*
  • Diosgenin / pharmacology
  • Down-Regulation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Melanins / biosynthesis*
  • Melanoma, Experimental / metabolism*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology
  • Solanum melongena / chemistry*
  • alpha-MSH / metabolism*

Substances

  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Melanins
  • Membrane Glycoproteins
  • Microphthalmia-Associated Transcription Factor
  • Plant Extracts
  • dioscin
  • alpha-MSH
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • Extracellular Signal-Regulated MAP Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
  • Diosgenin