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.

中文翻译：

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二邻羟基佳马醇通过蛋白激酶 A/cAMP 反应元件结合蛋白和细胞外信号调节激酶介导的小眼相关转录因子下调抑制 α-黑素细胞刺激激素刺激的 B16F10 黑色素瘤细胞和斑马鱼的黑色素生成


二邻羟基佳马醇 (DPHC) 是一种源自褐藻Ishige okamurae的海洋多酚化合物。此前的一项研究表明，DPHC 具有很强的蘑菇酪氨酸酶抑制活性。然而，DPHC在细胞水平上的抗黑素生成作用尚未见报道。本研究的目的是阐明DPHC在小鼠黑色素瘤细胞（B16F10）和斑马鱼模型中的黑色素生成抑制作用及其分子机制。 DPHC 显着抑制 α-黑素细胞刺激激素 (α-MSH) 刺激的 B16F10 细胞中的酪氨酸酶活性和黑色素含量，且呈剂量依赖性。这种多酚化合物还通过减弱 cAMP 依赖性蛋白激酶 A 的磷酸化来抑制 cAMP 反应元件结合蛋白 (CREB) 的磷酸化表达，从而导致 MITF 表达水平降低。此外，DPHC 通过促进细胞外信号调节激酶的磷酸化来下调 MITF 蛋白表达水平。它还抑制 α-MSH 刺激的 B16F10 细胞中的酪氨酸酶、酪氨酸酶相关蛋白 1 (TRP-1) 和 TRP-2。在使用斑马鱼的体内研究中，DPHC 还以剂量依赖性方式显着抑制黑色素合成。这些结果表明，DPHC在体外和斑马鱼体内均能有效抑制黑色素瘤细胞的黑色素生成，表明DPHC可作为皮肤美白剂应用于医药和药妆领域。