Abstract：
Hirsutanone (Hir) and oregonin (Ore) are diarylheptanoids isolated from the bark of Alnus japonica. In this study, we investigated the anti-melanogenic activity of Hir and Ore in B16-F1 murine melanoma and normal human epidermal melanocytes (HEMn-DP) and elucidated the mechanisms of action. In B16-F1 cells, Hir and Ore suppressed melanin synthesis induced by α-melanocyte-stimulating hormone (α-MSH) without cytotoxicity. The inhibitory effect of Hir on melanin synthesis was much stronger than that of Ore. In addition, Hir reduced melanin content in HEMn-DP cells. As tyrosinase is a key enzyme in melanin synthesis, the effect of Hir on tyrosinase activity was assessed. The results demonstrated that Hir partially decreased tyrosinase activity and intracellular tyrosinase activity. Moreover, Hir suppressed the protein expression of melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, leading to reduced melanin biosynthesis. Hir also led to the suppression of cAMP response element-binding protein (CREB) phosphorylation and microphthalmia-associated transcription factor (MITF) expression, which control the expression of melanogenic enzymes. These results suggest that Hir suppressed melanin synthesis by dual inhibition of tyrosinase activity and the CREB/MITF pathway leading to the expression of melanogenic enzymes and may be a potent cosmetic and therapeutic agent for hyperpigmentation disorders.
摘要：
Hirsutanone（Hir）和oregonin（Ore）是从Alnusjaponica的树皮中分离出的二芳基庚类化合物。在这项研究中,我们研究了Hir和Ore在B16-F1鼠黑色素瘤和正常人表皮黑素细胞（HEMn-DP）中的抗黑色素生成活性，并阐明了作用机制。在B16-F1细胞中，Hir和Ore抑制了α-黑素细胞刺激激素（α-MSH）诱导的黑色素合成，而没有细胞毒性。Hir对黑色素合成的抑制作用明显强于Ore。此外,Hir降低HEMn-DP细胞中的黑色素含量。酪氨酸酶是黑色素合成的关键酶,评估了Hir对酪氨酸酶活性的影响。结果表明，Hir部分降低了酪氨酸酶活性和细胞内酪氨酸酶活性。此外，Hir抑制了黑色素生成酶的蛋白表达，包括酪氨酸酶,酪氨酸酶相关蛋白（TRP）-1和TRP-2，导致黑色素生物合成减少。Hir还导致cAMP反应元件结合蛋白（CREB）磷酸化和小眼症相关转录因子（MITF）表达的抑制，控制黑色素生成酶的表达。这些结果表明，Hir通过双重抑制酪氨酸酶活性和CREB/MITF途径来抑制黑色素合成，从而导致黑色素生成酶的表达，并且可能是色素沉着过度症的有效化妆品和治疗剂。
