Anti-Melanogenic Activities of Heracleum moellendorffii via ERK1/2-Mediated MITF Downregulation

Int J Mol Sci. 2016 Nov 4;17(11):1844. doi: 10.3390/ijms17111844.

Abstract

In this study, the anti-melanogenic effects of Heracleum moellendorffii Hance extract (HmHe) and the mechanisms through which it inhibits melanogenesis in melan-a cells were investigated. Mushroom tyrosinase (TYR) activity and melanin content as well as cellular tyrosinase activity were measured in the cells. mRNA and protein expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TYRP-1) and -2 were also examined. The results demonstrate that treatment with HmHe significantly inhibits mushroom tyrosinase activity. Furthermore, HmHe also markedly inhibits melanin production and intracellular tyrosinase activity. By suppressing the expression of TYR, TYRP-1, TYRP-2, and MITF, HmHe treatment antagonized melanin production in melan-a cells. Additionally, HmHe interfered with the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, with reversal of HmHe-induced melanogenesis inhibition after treatment with specific inhibitor U0126. In summary, HmHe can be said to stimulate ERK1/2 phosphorylation and subsequent degradation of MITF, resulting in suppression of melanogenic enzymes and melanin production, possibly due to the presence of polyphenolic compounds.

Keywords: ERK; Heracleum moellendorffii; MITF; melanin; melanogenesis; tyrosinase.

MeSH terms

  • Agaricales / chemistry
  • Animals
  • Butadienes / pharmacology
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / metabolism
  • Gene Expression Regulation
  • Heracleum / chemistry*
  • Indoles / antagonists & inhibitors*
  • Indoles / metabolism
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis
  • Melanocytes / cytology
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / metabolism
  • Nitriles / pharmacology
  • Oxidoreductases / antagonists & inhibitors
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Signal Transduction

Substances

  • Butadienes
  • Enzyme Inhibitors
  • Fungal Proteins
  • Indoles
  • Melanins
  • Membrane Glycoproteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Nitriles
  • Plant Extracts
  • Protective Agents
  • U 0126
  • melanogen
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • Monophenol Monooxygenase
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Intramolecular Oxidoreductases
  • dopachrome isomerase