5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety

<b>Background/Objectives:</b> This study aims to investigate the effects of 5,7-dihydroxy-4-methylcoumarin (5,7D-4MC) on melanogenesis in B16F10 murine melanoma cells and to evaluate its safety as a potential ingredient for functional cosmetics and therapeutic agents targeting pigmentati...

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Main Authors: Ye-Jin Lee, Yang Xu, Chang-Gu Hyun
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/4/463
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author Ye-Jin Lee
Yang Xu
Chang-Gu Hyun
author_facet Ye-Jin Lee
Yang Xu
Chang-Gu Hyun
author_sort Ye-Jin Lee
collection DOAJ
description <b>Background/Objectives:</b> This study aims to investigate the effects of 5,7-dihydroxy-4-methylcoumarin (5,7D-4MC) on melanogenesis in B16F10 murine melanoma cells and to evaluate its safety as a potential ingredient for functional cosmetics and therapeutic agents targeting pigmentation-related disorders. <b>Method:</b> The cytotoxicity of 5,7D-4MC was assessed using an MTT assay, and melanin content and tyrosinase activity were measured at different concentrations (25, 50, 100 µM). Western blot analyses were conducted to evaluate the expression of key melanogenesis-related proteins (TYR, TRP-1, TRP-2, and MITF) and to investigate the regulation of major signaling pathways, including PKA/cAMP, GSK3β, and PI3K/AKT. Additionally, a human primary skin irritation test was performed on 32 participants to assess the dermatological safety of 5,7D-4MC. <b>Results:</b> 5,7D-4MC did not affect cell viability at concentrations below 100 µM and significantly promoted melanin production in a dose-dependent manner. Tyrosinase activity and the expression levels of melanogenic proteins increased significantly following 5,7D-4MC treatment. PKA and GSK3β pathways were activated, while the PI3K/AKT pathway was downregulated. The skin irritation test showed that 5,7D-4MC exhibited low irritation potential at concentrations of 50 µM and 100 µM. <b>Conclusions:</b> 5,7D-4MC enhances melanogenesis and demonstrates low skin irritation, making it a promising candidate for therapeutic applications in treating hypopigmentation disorders, such as vitiligo, as well as a functional cosmetic ingredient. However, further studies involving human melanocytes and clinical trials are required to validate their efficacy.
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spelling doaj-art-30901ec423734979b516aaba18129d5c2025-08-20T02:28:18ZengMDPI AGPharmaceuticals1424-82472025-03-0118446310.3390/ph180404635,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin SafetyYe-Jin Lee0Yang Xu1Chang-Gu Hyun2Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of KoreaJeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of KoreaJeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of Korea<b>Background/Objectives:</b> This study aims to investigate the effects of 5,7-dihydroxy-4-methylcoumarin (5,7D-4MC) on melanogenesis in B16F10 murine melanoma cells and to evaluate its safety as a potential ingredient for functional cosmetics and therapeutic agents targeting pigmentation-related disorders. <b>Method:</b> The cytotoxicity of 5,7D-4MC was assessed using an MTT assay, and melanin content and tyrosinase activity were measured at different concentrations (25, 50, 100 µM). Western blot analyses were conducted to evaluate the expression of key melanogenesis-related proteins (TYR, TRP-1, TRP-2, and MITF) and to investigate the regulation of major signaling pathways, including PKA/cAMP, GSK3β, and PI3K/AKT. Additionally, a human primary skin irritation test was performed on 32 participants to assess the dermatological safety of 5,7D-4MC. <b>Results:</b> 5,7D-4MC did not affect cell viability at concentrations below 100 µM and significantly promoted melanin production in a dose-dependent manner. Tyrosinase activity and the expression levels of melanogenic proteins increased significantly following 5,7D-4MC treatment. PKA and GSK3β pathways were activated, while the PI3K/AKT pathway was downregulated. The skin irritation test showed that 5,7D-4MC exhibited low irritation potential at concentrations of 50 µM and 100 µM. <b>Conclusions:</b> 5,7D-4MC enhances melanogenesis and demonstrates low skin irritation, making it a promising candidate for therapeutic applications in treating hypopigmentation disorders, such as vitiligo, as well as a functional cosmetic ingredient. However, further studies involving human melanocytes and clinical trials are required to validate their efficacy.https://www.mdpi.com/1424-8247/18/4/463B16F105,7-dihydroxy-4-methylcoumarinhypopigmentationmelanogenesisprimary skin irritation testsignaling pathway
spellingShingle Ye-Jin Lee
Yang Xu
Chang-Gu Hyun
5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety
Pharmaceuticals
B16F10
5,7-dihydroxy-4-methylcoumarin
hypopigmentation
melanogenesis
primary skin irritation test
signaling pathway
title 5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety
title_full 5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety
title_fullStr 5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety
title_full_unstemmed 5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety
title_short 5,7-Dihydroxy-4-Methylcoumarin as a Functional Compound for Skin Pigmentation and Human Skin Safety
title_sort 5 7 dihydroxy 4 methylcoumarin as a functional compound for skin pigmentation and human skin safety
topic B16F10
5,7-dihydroxy-4-methylcoumarin
hypopigmentation
melanogenesis
primary skin irritation test
signaling pathway
url https://www.mdpi.com/1424-8247/18/4/463
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