Department of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, Republic of Korea.
Department of Foodservice Management, Woosong University, Daejeon 34606, Republic of Korea.
Biomed Pharmacother. 2018 Aug;104:582-589. doi: 10.1016/j.biopha.2018.05.083. Epub 2018 May 25.
Hyperpigmentation disorders of the skin adversely influence the quality of life. We previously demonstrated the hypopigmenting properties of the ethanolic extract from Sargassum serratifolium and identified sargaquinoic acid (SQA) as an active component. The current study aims to investigate the hypopigmenting action of SQA in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. SQA attenuated cellular melanin synthesis by inhibiting the expression of the melanogenic enzymes, including tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and TRP2. SQA also inhibited cellular TYR activity in a dose-dependent manner. Reduced intracellular cAMP accumulation by SQA treatment resulted in the suppressed phosphorylation of cAMP-responsive element-binding protein (CREB), leading to the downregulation of microphthalmia-associated transcription factor (MITF) in α-MSH-stimulated B16F10 cells. SQA increased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and MITF (Ser73), inducing proteasomal degradation of MITF. SQA showed high binding affinity to the cAMP binding domain of PKA; the direct binding of SQA to PKA may exert an additional inhibitory effect on the PKA-dependent CREB activation. Our data demonstrated that SQA suppressed melanin production through the cAMP/CREB- and ERK1/2-mediated downregulation of MITF in α-MSH-stimulated B16F10 cells and SQA has a potential therapeutic agent for the treatment of skin hyperpigmentation disorders.
皮肤色素沉着障碍会降低生活质量。我们之前已经证实了皱波角叉菜乙醇提取物的皮肤美白作用，并鉴定出 Sargaquinoic acid（SQA）是其有效成分之一。本研究旨在探讨 SQA 在α-促黑素细胞激素（α-MSH）刺激的 B16F10 细胞中对黑色素生成的抑制作用。SQA 通过抑制黑素生成酶的表达，包括酪氨酸酶（TYR）、酪氨酸酶相关蛋白 1（TRP1）和 TRP2，来减少细胞黑色素的合成。SQA 还呈剂量依赖性地抑制细胞 TYR 活性。SQA 处理导致细胞内环磷酸腺苷（cAMP）积累减少，从而抑制 cAMP 反应元件结合蛋白（CREB）的磷酸化，导致在 α-MSH 刺激的 B16F10 细胞中小眼畸形相关转录因子（MITF）下调。SQA 增加细胞外信号调节激酶（ERK1/2）和 MITF（Ser73）的磷酸化，诱导 MITF 的蛋白酶体降解。SQA 与蛋白激酶 A（PKA）的 cAMP 结合域具有高结合亲和力；SQA 与 PKA 的直接结合可能对 PKA 依赖性 CREB 激活产生额外的抑制作用。我们的数据表明，SQA 通过 cAMP/CREB 和 ERK1/2 介导的 MITF 下调抑制 α-MSH 刺激的 B16F10 细胞中的黑色素生成，SQA 可能是治疗皮肤色素沉着障碍的潜在治疗药物。
