Hypopigmentary Action of Dihydropyranocoumarin D2, a Decursin Derivative, as a MITF-Degrading Agent

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• 作者：Dong-Seok Kim ; So-Hee Park ; Hyun-Kyung Lee ; Soo-Jin Choo ; Jee Hyun Lee ; Gyu Yong Song ; Ick-Dong Yoo ; Sun-Bang Kwon ; Jung-Im Na ; Kyoung-Chan Park
• 刊名：Journal of Natural Products
• 出版年：2010
• 出版时间：May 28, 2010
• 年：2010
• 卷：73
• 期：5
• 页码：797-800
• 全文大小：222K
• 年卷期：v.73,no.5(May 28, 2010)
• ISSN：1520-6025

文摘

In this study, the decursin derivative dihydropyranocoumarin D2 (1) was selected for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). The results showed that 1 effectively inhibited melanin synthesis in a concentration-dependent manner, but that it did not inhibit tyrosinase in a cell-free system. In addition, the changes in ERK, Akt, and microphthalmia-associated transcription factor (MITF) in response to treatment with 1 were assessed. The results revealed that ERK was dramatically up-regulated and MITF was down-regulated in response to treatment with 1, but that Akt was unchanged. Therefore, the effects of 1 on melanogenesis were examined in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway). PD98059 restored hypopigmentation and the down-regulation of MITF induced by 1. Finally, MITF down-regulation by 1 was clearly restored by both chloroquine, a lysosomal proteolysis inhibitor, and MG132, a proteasome inhibitor.