S-(-)-10,11-dihydroxyfarnesoic acid methyl ester inhibits melanin synthesis in murine melanocyte cells

Int J Mol Sci. 2014 Jul 18;15(7):12750-63. doi: 10.3390/ijms150712750.

Abstract

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029, exhibits potent antimelanogenic activity. We isolated and purified an active metabolite and identified it as S-(-)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin synthesis, we first measured the size of the melanin biosynthesis inhibition zone caused by dhFAME. dhFAME also showed inhibitory activity against mushroom tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition activity was also confirmed by zymography. In addition, we showed that dhFAME strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse-transcription polymerase chain reaction and showed that treatment of Melan-a cells with 35 μM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together, these results indicate that dhFAME is a potent inhibitor of melanin synthesis that can potentially be used for cosmetic biomaterial(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Beauveria / chemistry
  • Cell Line
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Juvenile Hormones / isolation & purification
  • Juvenile Hormones / pharmacology*
  • Melanins / biosynthesis*
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Juvenile Hormones
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • RNA, Messenger
  • Oxidoreductases
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • Intramolecular Oxidoreductases
  • dopachrome isomerase