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Int. J. Mol. Sci. 2015, 16(4), 8772-8788;

Melanogenesis-Inducing Effect of Cirsimaritin through Increases in Microphthalmia-Associated Transcription Factor and Tyrosinase Expression

Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
School of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Korea
Department of Research and Development, Erina Co., Inc., 1-9-2 Hagashi-Shinbashi, Minato-ku, Tokyo 105-0021, Japan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Ritva Tikkanen
Received: 26 February 2015 / Accepted: 9 April 2015 / Published: 20 April 2015
(This article belongs to the Section Biochemistry)
PDF [797 KB, uploaded 20 April 2015]


The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments. View Full-Text
Keywords: cirsimaritin; melanogenesis; melanoma; tyrosinase; MITF cirsimaritin; melanogenesis; melanoma; tyrosinase; MITF

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Kim, H.J.; Kim, I.S.; Dong, Y.; Lee, I.-S.; Kim, J.S.; Kim, J.-S.; Woo, J.-T.; Cha, B.-Y. Melanogenesis-Inducing Effect of Cirsimaritin through Increases in Microphthalmia-Associated Transcription Factor and Tyrosinase Expression. Int. J. Mol. Sci. 2015, 16, 8772-8788.

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