Inhibitory effects of 4-n-butylresorcinol on tyrosinase activity and melanin synthesis
Inhibitory effects of 4-n-butylresorcinol on tyrosinase activity and melanin synthesis
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DOI：
10.1248/bpb.28.2216
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发表时间：
2005-12-01
影响因子：
2
通讯作者：
Park, KC
中科院分区：
文献类型：
--
作者：
Kim, DS;Kim, SY;Park, KC
在这项研究中，我们研究了4-正丁基间苯二酚对自然永生化的小鼠黑素细胞系Mel-Ab黑素合成的影响。我们的结果表明，4-正丁基间苯二酚以浓度依赖的方式显著抑制黑色素合成。此外，它还被发现抑制酪氨酸酶的活性，酪氨酸酶是黑素生成的限速酶。已有报道指出，细胞外信号调节激酶(ERK)或Akt的激活通过下调小眼球相关转录因子(MITF)的表达来减少黑色素的合成。因此，我们研究了4-正丁基间苯二酚对ERK和Akt信号通路的影响。4-正丁基间苯二酚不诱导ERK、Akt激活或MITF降解，也不影响cAMP反应元件结合蛋白(CREB)的磷酸化，从而刺激MITF的表达。相反，在无细胞体系中，4-正丁基间苯二酚强烈降低酪氨酸酶活性。此外，4-正丁基间苯二酚与Hin okitiol联合使用时表现出相加效应，可降低MITF的表达。这些结果表明，4-正丁基间苯二酚对酪氨酸酶的直接抑制作用是其色素减退作用的结果。
In this study, we investigated the effects of 4-n-butylresorcinol on melanogenesis in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that 4-n-butylresorcinol significantly inhibits melanin synthesis in a concentration-dependent manner. In addition, it was also found to inhibit the activity of tyrosinase, the rate-limiting melanogenic enzyme. Several reports have indicated that the activation of extracellular signal-regulated kinase (ERK) or of Akt reduces melanin synthesis via microphthalmia-associated transcription factor (MITF) down-regulation. Accordingly, we examined the effects of 4-n-butylresorcinol on the ERK and Akt signaling pathways. 4-n-Butylresorcinol did not induce ERK, Akt activation, or MITF degradation, and had no effect on cAMP response element binding protein (CREB) phosphorylation, which stimulates MITF expression. In contrast, 4-n-butylresorcinol strongly reduced tyrosinase activity in a cell-free system. Moreover, 4-n-butylresorcinol showed an additive effect in combination with hinokitiol, which reduces MITF expression. These results show that the hypopigmentary effect of 4-n-butylresorcinol results from its direct inhibition of tyrosinase.