Kim Hyo Jung, Yonezawa Takayuki, Teruya Toshiaki, Woo Je-Tae, Cha Byung-Yoon
Research Institute for Biological Functions, Chubu University, Kasugai, Aichi, Japan.
Photochem Photobiol. 2015 Mar-Apr;91(2):379-86. doi: 10.1111/php.12400. Epub 2015 Jan 12.
Nobiletin is a unique flavonoid having polymethoxy groups and has exhibited anti-inflammatory and antiobesity effects. Here, we examined the inhibition of nobiletin on melanogenesis induced by endothelin-1 (ET) and stem cell factor (SCF) in normal human melanocytes. Nobiletin dose dependently reduced ET plus SCF-stimulated tyrosinase activity without causing cytotoxicity. Nobiletin reduced cAMP-response element-binding protein (CREB) phosphorylation and microphthalmia-associated transcription factor (MITF) expression, which is a key transcription factor for tyrosinase expression in pigmentation induced by ET plus SCF stimulation. Nobiletin treatment effectively decreased ET plus SCF-induced Raf-1, MEK and ERK1/2 phosphorylation and also downregulated the forskolin-induced phosphorylation of CREB. Furthermore, nobiletin inhibited ET plus SCF-triggered production of melanin and expression of MITF/tyrosinase in a three-dimensional human epidermal model. In accordance with protein expression, the expression of genes related to the pigmentation was also increased in the cells stimulated with ET plus SCF and the cotreatment with nobiletin decreased obviously the ET plus SCF-triggered gene expressions of tyrosinase, PMEL, TRP1 and MITF. Nobiletin contributes to hypopigmentation by downregulating MITF and tyrosinase expression through reduced Raf-1 phosphorylation. Our findings implicate nobiletin as a potential new whitening agent.
川陈皮素是一种具有多甲氧基的独特类黄酮，已显示出抗炎和抗肥胖作用。在此，我们研究了川陈皮素对正常人黑素细胞中内皮素 -1（ET）和干细胞因子（SCF）诱导的黑素生成的抑制作用。川陈皮素剂量依赖性地降低了ET加SCF刺激的酪氨酸酶活性，且未引起细胞毒性。川陈皮素降低了cAMP反应元件结合蛋白（CREB）的磷酸化以及小眼畸形相关转录因子（MITF）的表达，MITF是ET加SCF刺激诱导色素沉着过程中酪氨酸酶表达的关键转录因子。川陈皮素处理有效地降低了ET加SCF诱导的Raf-1、MEK和ERK1/2的磷酸化，并且还下调了福斯可林诱导的CREB磷酸化。此外，川陈皮素在三维人表皮模型中抑制了ET加SCF引发的黑色素生成以及MITF/酪氨酸酶的表达。与蛋白质表达一致，在用ET加SCF刺激的细胞中，与色素沉着相关的基因表达也增加，而川陈皮素的联合处理明显降低了ET加SCF引发的酪氨酸酶、PMEL、TRP1和MITF的基因表达。川陈皮素通过降低Raf-1磷酸化来下调MITF和酪氨酸酶的表达，从而有助于色素减退。我们的研究结果表明川陈皮素是一种潜在的新型美白剂。
