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Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression

1
Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea
2
Bio-Center, Gyeonggido Business & Science Accelerator (GBSA), Suwon 16229, Korea
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(4), 87; https://doi.org/10.3390/antiox8040087
Received: 7 March 2019 / Revised: 29 March 2019 / Accepted: 2 April 2019 / Published: 4 April 2019
(This article belongs to the Special Issue Role of Flavonoids on Cell Signalling Pathways)
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Abstract

Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis. View Full-Text
Keywords: melanin; luteolin 7-sulfate; luteolin; tyrosinase; flavonoid melanin; luteolin 7-sulfate; luteolin; tyrosinase; flavonoid
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Lee, S.W.; Kim, J.H.; Song, H.; Seok, J.K.; Hong, S.S.; Boo, Y.C. Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression. Antioxidants 2019, 8, 87.

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