Diphlorethohydroxycarmalol (DPHC) is a marine polyphenolic compound derived from brown alga Ishige okamurae. A previously study has suggested that DPHC possesses strong mushroom
tyrosinase inhibitory activity. However, the anti-melanogenesis effect of DPHC has not been reported at cellular level. The objective of the present study was to clarify the melanogenesis inhibitory effect of DPHC and its molecular mechanisms in murine
melanoma cells (B16F10) and zebrafish model. DPHC significantly inhibited
tyrosinase activity and
melanin content dose-dependently in α-
melanocyte stimulating hormone (α-
MSH)-stimulated B16F10 cells. This polyphenolic compound also suppressed the expression of phosphorylation of
cAMP response element-binding protein (CREB) by attenuating phosphorylation of
cAMP-dependent protein kinase A, resulting in decreased MITF expression levels. Furthermore, DPHC downregulated
MITF protein expression levels by promoting the phosphorylation of
extracellular signal-regulated kinase. It also inhibited
tyrosinase,
tyrosinase-related
protein 1 (TRP-1), and TRP-2 in α-
MSH stimulated B16F10 cells. In in vivo studies using zebrafish, DPHC also markedly inhibited
melanin synthesis in a dose-dependent manner. These results demonstrate that DPHC can effectively inhibit melanogenesis in
melanoma cells in vitro and in zebrafish in vivo, suggesting that DPHC could be applied in fields of
pharmaceutical and
cosmeceuticals as a
skin-whitening agent. Significance of study: The present study showed for the first time that DPHC could inhibit a-
MSH-stimulated melanogenesis via PKA/CREB and ERK pathway in
melanoma cells. It also could inhibit pigmentation in vivo in a zebrafish model. This evidence suggests that DPHC has potential as a
skin whitening agent. Taken together, DPHC could be considered as a novel anti-melanogenic agent to be applied in cosmetic, food, and medical industry.