(E)-4-(3,4-Dimethoxyphenyl)but-3-en-1-ol Enhances Melanogenesis through Increasing Upstream Stimulating Factor-1-Mediated Tyrosinase Expression

PLoS One. 2015 Nov 4;10(11):e0141988. doi: 10.1371/journal.pone.0141988. eCollection 2015.

Abstract

We investigated the potential melanogenic effect of compounds from Zingiber cassumunar Roxb. Our data revealed that chloroform-soluble extract of Z. cassumunar enhanced melanin synthesis in B16F10 melanoma cells. Among the components of the chloroform extract, (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-ol (DMPB) increased melanogenesis in both B16F10 cells and human primary melanocytes. In B16F10 cells, DMPB enhanced the activation of ERK and p38, and the level of tyrosinase. Although the level of microphthalmia-associated transcription factor was unchanged in DMPB-treated B16F10 cells, DMPB increased levels and nuclear localization of upstream stimulating factor-1 (USF1). Consistently, DMPB-mediated melanin synthesis was diminished in USF1-knockdown cells. Furthermore, DMPB induced hyperpigmentation in brown guinea pigs in vivo. Together, these data suggest that DMPB may promote melanin synthesis via USF1 dependent fashion and could be used as a clinical therapeutic agent against hypopigmentation-associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butanols / chemistry
  • Butanols / isolation & purification
  • Butanols / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation / drug effects*
  • Guinea Pigs
  • Humans
  • Liquid-Liquid Extraction
  • Melanins / metabolism*
  • Melanocytes / cytology
  • Melanocytes / metabolism
  • Methanol / chemistry
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinases / metabolism
  • Monophenol Monooxygenase / chemistry
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism*
  • Pigmentation
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects
  • Upstream Stimulatory Factors / antagonists & inhibitors
  • Upstream Stimulatory Factors / genetics
  • Upstream Stimulatory Factors / metabolism*
  • Zingiber officinale / chemistry*
  • Zingiber officinale / metabolism

Substances

  • Butanols
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • RNA, Small Interfering
  • Upstream Stimulatory Factors
  • Usf1 protein, mouse
  • 4-(3',4'-dimethoxyphenyl)but-3-en-1-ol
  • Monophenol Monooxygenase
  • Mitogen-Activated Protein Kinases
  • Methanol

Grants and funding

The work was supported by the following: National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP), grant number: 2012R1A5A1048236 (URL: www.nrf.re.kr); the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea, grant number: HI12C0050 (URL: http://www.mw.go.kr); and the Ministry of Science, ICT and Future Planning (NRF2012M3A9C4048761). The funders had roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.