Dual Inhibition of gamma-Oryzanol on Cellular Melanogenesis: Inhibition of Tyrosinase Activity and Reduction of Melanogenic Gene Expression by a Protein Kinase A-Dependent Mechanism

作者：Jun Hee jin; Lee Ji Hae; Cho Bo Ram; Seo Woo Duck; Kang Hang Won; Kim Dong Woo; Cho Kang Jin; Lee Sung Joon^*

来源：Journal of Natural Products, 2012, 75(10): 1706-1711.

DOI：10.1021/np300250m

The in vitro effects on melanogenesis of gamma-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 mu M, 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 PICA 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.

• 出版日期2012-10