Induction of melanogenesis by 4'-O-methylated flavonoids in B16F10 melanoma cells
Induction of melanogenesis by 4'-O-methylated flavonoids in B16F10 melanoma cells
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DOI：
10.1007/s11418-012-0727-y
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发表时间：
2013-10-01
影响因子：
3.3
通讯作者：
Nagaoka, Yasuo
中科院分区：
文献类型：
--
作者：
Horibe, Ippei;Satoh, Yudai;Nagaoka, Yasuo
控制黑素生成的试剂对于改善皮肤和毛发的色素沉着病症的化妆品的开发是需要的。在这项研究中，我们检查和评估黄酮类化合物对黑素生成细胞模型，小鼠B16 F10黑色素瘤细胞中黑素生成的影响。在该研究过程中，我们发现，在含有10 μ M的4’-O-甲基化类黄酮、薯蓣皂苷（4’-O-甲基毛地黄黄酮）、金合欢素（4’-O-甲基芹菜素）或山奈素（4’-O-甲基山奈酚）的培养基中孵育细胞，使细胞的黑色素含量比对照细胞高3- 7倍。浓度依赖性试验显示，20 μ M金合欢素显示出最高的效果，比溶媒高33倍。另一方面，相应的4 '-OH-型黄酮类化合物，毛地黄黄酮，芹菜素和山奈酚，有一个显着较小的影响。此外，通过评估黑素生成蛋白，我们发现用4 '-O-甲基化类黄酮处理的细胞显示出更高的酪氨酸酶活性，以及酪氨酸酶表达的上调，之前是cAMP反应元件结合蛋白（CREB）和细胞外信号调节激酶1和2型（ERK 1/2）的激活。这些结果表明，黄酮类化合物的4 '-O-甲基通过上调小鼠B16 F10黑色素瘤细胞中磷酸化CREB激活其主要信号转导途径，在诱导黑色素生成中起重要作用。
Agents to control melanogenesis are in demand for the development of cosmetics to improve pigmentation disorders of skin and hair. In this study, we examined and evaluated the effects of flavonoids on melanogenesis in the melanogenic cells model, murine B16F10 melanoma cells. In the course of this study, we found that incubation of the cells in a medium containing 10 mu M of the 4'-O-methylated flavonoids, diosmetin (4'-O-methylluteolin), acacetin (4'-O-methylapigenin) or kaempferide (4'-O-methylkaempferol), increased the melanin contents of the cells 3- to 7-fold higher than the control cells. The concentration-dependence test revealed that 20 mu M acacetin showed the highest effect, up to 33-fold higher than the vehicle. On the other hand, the corresponding 4'-OH-type flavonoids, luteolin, apigenin and kaempferol, had a significantly smaller effect. Furthermore, by evaluating the melanogenic proteins, we found that the cells treated with 4'-O-methylated flavonoids showed higher tyrosinase activity, as well as upregulation of tyrosinase expression, preceded by activation of cAMP response element binding protein (CREB) and extracellular signal-regulated kinases types 1 and 2 (ERK1/2). These results indicate that the 4'-O-methyl group of flavonoids plays an important role in the induction of melanogenesis by activating its major signal transduction pathway through the upregulation of phospho-CREB in murine B16F10 melanoma cells.