Lee Seok Won, Kim Jae Heon, Song Hyerim, Seok Jin Kyung, Hong Seong Su, Boo Yong Chool
Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea.
Bio-Center, Gyeonggido Business & Science Accelerator (GBSA), Suwon 16229, Korea.
Antioxidants (Basel). 2019 Apr 4;8(4):87. doi: 10.3390/antiox8040087.
Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis.
具有抗黑色素生成活性的抗氧化剂可能有助于减轻皮肤色素沉着紊乱。在之前的一项研究中，从海洋植物滨旋花中分离出的木犀草素7 - 硫酸盐被证明能抑制细胞黑色素合成。本研究的目的是研究其作用机制，重点关注细胞中酪氨酸酶（TYR）表达的调控。使用小鼠黑色素瘤B16 - F10细胞和原代人表皮黑素细胞（HEM）进行基于细胞的实验。在B16 - F10细胞中，木犀草素7 - 硫酸盐相比木犀草素显示出更低的毒性。在无毒浓度范围内，木犀草素7 - 硫酸盐减弱了由α - 黑素细胞刺激激素或福斯高林刺激引起的黑色素合成。木犀草素7 - 硫酸盐在mRNA和蛋白质水平上减弱了福斯高林诱导的小眼畸形相关转录因子（MITF）和TYR的表达。它还减弱了福斯高林刺激的环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化。木犀草素7 - 硫酸盐也减弱了原代HEM中的黑色素合成。本研究表明，木犀草素7 - 硫酸盐通过干预CREB和MITF介导的信号通路减弱TYR基因表达，导致黑色素合成减少。
