Dual inhibition of γ-oryzanol on cellular melanogenesis: Inhibition of tyrosinase activity and reduction of melanogenic gene expression by a protein kinase a-dependent mechanism

Hee Jin Jun, Ji Hae Lee, Bo Ram Cho, Woo Duck Seo, Hang Won Kang, Dong Woo Kim, Kang Jin Cho, Sung Joon Lee

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The in vitro effects on melanogenesis of γ-oryzanol (1), a rice bran-derived phytosterol, were investigated. The melanin content in B16F1 cells was significantly and dose-dependently reduced (-13% and -28% at 3 and 30 μM, respectively). Tyrosinase enzyme activity was inhibited by 1 both in a cell-free assay and when analyzed based on the measurement of cellular tyrosinase activity. Transcriptome analysis was performed to investigate the biological pathways altered by 1, and it was found that gene expression involving protein kinase A (PKA) signaling was markedly altered. Subsequent analyses revealed that 1 stimulation in B16 cells reduced cytosolic cAMP concentrations, PKA activity (-13% for cAMP levels and -40% for PKA activity), and phosphorylation of the cAMP-response element binding protein (-57%), which, in turn, downregulated the expression of microphthalmia-associated transcription factor (MITF; -59% for mRNA and -64% for protein), a key melanogenic gene transcription factor. Accordingly, tyrosinase-related protein 1 (TRP-1; -69% for mRNA and -82% for protein) and dopachrome tautomerase (-51% for mRNA and -92% for protein) in 1-stimulated B16F1 cells were also downregulated. These results suggest that 1 has dual inhibitory activities for cellular melanogenesis by inhibiting tyrosinase enzyme activity and reducing MITF and target genes in the PKA-dependent pathway.

Original languageEnglish
Pages (from-to)1706-1711
Number of pages6
JournalJournal of Natural Products
Volume75
Issue number10
DOIs
Publication statusPublished - 2012 Oct 26

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Dual inhibition of γ-oryzanol on cellular melanogenesis: Inhibition of tyrosinase activity and reduction of melanogenic gene expression by a protein kinase a-dependent mechanism'. Together they form a unique fingerprint.

Cite this