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

Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from <i>Phyllospadix iwatensis</i> Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim...

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Main Authors: Seok Won Lee, Jae Heon Kim, Hyerim Song, Jin Kyung Seok, Seong Su Hong, Yong Chool Boo
Format: Article
Language:English
Published: MDPI AG 2019-04-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/8/4/87
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author Seok Won Lee
Jae Heon Kim
Hyerim Song
Jin Kyung Seok
Seong Su Hong
Yong Chool Boo
author_facet Seok Won Lee
Jae Heon Kim
Hyerim Song
Jin Kyung Seok
Seong Su Hong
Yong Chool Boo
author_sort Seok Won Lee
collection DOAJ
description Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from <i>Phyllospadix iwatensis</i> 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 &#945;-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.
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spelling doaj.art-81f1ac60d58449bc9fa140a1cecabdcc2023-09-02T18:32:57ZengMDPI AGAntioxidants2076-39212019-04-01848710.3390/antiox8040087antiox8040087Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase ExpressionSeok Won Lee0Jae Heon Kim1Hyerim Song2Jin Kyung Seok3Seong Su Hong4Yong Chool Boo5Department 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, KoreaDepartment 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, KoreaDepartment 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, KoreaDepartment 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, KoreaBio-Center, Gyeonggido Business &amp; Science Accelerator (GBSA), Suwon 16229, KoreaDepartment 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, KoreaAntioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from <i>Phyllospadix iwatensis</i> 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 &#945;-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.https://www.mdpi.com/2076-3921/8/4/87melaninluteolin 7-sulfateluteolintyrosinaseflavonoid
spellingShingle Seok Won Lee
Jae Heon Kim
Hyerim Song
Jin Kyung Seok
Seong Su Hong
Yong Chool Boo
Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
Antioxidants
melanin
luteolin 7-sulfate
luteolin
tyrosinase
flavonoid
title Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
title_full Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
title_fullStr Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
title_full_unstemmed Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
title_short Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
title_sort luteolin 7 sulfate attenuates melanin synthesis through inhibition of creb and mitf mediated tyrosinase expression
topic melanin
luteolin 7-sulfate
luteolin
tyrosinase
flavonoid
url https://www.mdpi.com/2076-3921/8/4/87
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