Daphnetin is a dehydroxylated derivative of coumarin isolated from Daphne species. However, the effect of daphnetin on melanogenesis has not been elucidated. This study aims to investigate the inhibitory effect of daphnetin on melanogenesis in α-melanocyte stimulating hormone (α-MSH)-treated B16F10 cells and its potential mechanism. Melanin content analysis and cellular tyrosinase activity assay showed that daphnetin inhibited melanin biosynthesis in α-MSH-treated B16F10 cells. Immunoblotting and qRT-PCR also indicated that daphnetin suppressed the expression of microphthalmia-associated transcription factor, a mastering transcription factor of melanogenesis and its downstream melanogenic enzymes including tyrosinase and tyrosinase-related proteins. Moreover, daphnetin downregulated the phosphorylation of PKA, ERK, MSK1, and CREB. Additionally, daphnetin inhibited melanin synthesis in UVB-irradiated HaCaT conditioned medium system suggesting that daphnetin has potential as an antipigmentation activity in a physiological skin condition. Our data propose that daphnetin inhibits melanogenesis via modulating both the PKA/CREB and the ERK/MSK1/CREB pathways.

Purpose: This study aims to understand the role Angelica gigas (A. gigas) Nakai root extract (AGNRE) fermented with Jeju lava seawater in collagenase suppression in human dermal fibroblasts, and identify the major active compound responsible for it suppressive effect. Methods: AGNREs were prepared by fermentation with Jeju lava water at low temperature and analyzed for identifying the major active compound in these fermented root extracts using high-performance liquid chromatography (HPLC). Water-soluble tetrazolium salt (WST-1) assay and real-time polymerase chain reaction (qRT-PCR) were performed to investigate the cell viability and expression level of collagenase gene. Comparative experiments were performed using AGNREs and decursin to confirm the downregulation of collagenase expression and analyze the correlation between them. Results: HPLC analysis revealed decursin to be the major active compound in AGNREs. Analysis of data obtained by WST-1 assays at concentration of 200 μg/mL for AGNREs and <20 μM for decursin did not show any cytotoxicity in human dermal fibroblasts. qRT-PCR analysis revealed that AGNREs as well as decursin downregulated the expression of matrix metalloproteinases-3 (MMP3) gene in human dermal fibroblasts. Conclusion: These analyses suggest that AGNREs fermented with Jeju lava water as well as decursin isolated from these extracts hold a great potential to be applied as functional anti-wrinkle agent in cosmetic.