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Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocyt...

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Autores principales: Wang, Yan, Hao, Mi-Mi, Sun, Ying, Wang, Li-Feng, Wang, Hao, Zhang, Yan-Jun, Li, Hong-Yan, Zhuang, Peng-Wei, Yang, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017046/
https://www.ncbi.nlm.nih.gov/pubmed/29300356
http://dx.doi.org/10.3390/molecules23010106
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author Wang, Yan
Hao, Mi-Mi
Sun, Ying
Wang, Li-Feng
Wang, Hao
Zhang, Yan-Jun
Li, Hong-Yan
Zhuang, Peng-Wei
Yang, Zhen
author_facet Wang, Yan
Hao, Mi-Mi
Sun, Ying
Wang, Li-Feng
Wang, Hao
Zhang, Yan-Jun
Li, Hong-Yan
Zhuang, Peng-Wei
Yang, Zhen
author_sort Wang, Yan
collection PubMed
description When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocytes to produce melanin. Meanwhile, the Keap1-Nrf2/ARE pathway, which removes ROS, is activated at increased ROS levels, and antioxidant compounds facilitates the dissociation of Nrf2. In this study, we explored the possible suppressing effects of antioxidant compounds and tyrosine inhibitors on melanin formation and the promotory effects of these compounds on ROS scavenging. The antioxidant activity of glabridin (GLA), resveratrol (RES), oxyresveratrol (OXYR), and phenylethylresorcinol (PR) were investigated via the stable free radical 2,2-diphenyl-1-picrylhydrazyl method. The inhibitory effects of the four compounds and their mixtures on tyrosinase were evaluated. l-Tyrosine or 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA) was used as a substrate. The results showed that all mixtures did not exhibit synergistic effects with the l-tyrosine as a substrate, suggesting that l-tyrosine is not suitable as a substrate. However, the mixtures of “GLA:RES,” “GLA:OXYR,” “OXYR:RES,” and “PR:RES” demonstrated synergistic effects (CI < 0.9, p < 0.05), whereas “GLA:RES” and “PR:OXYR” indicated an additive effect (0.9 ditive1, p < 0.05). Furthermore, we used a molecular docking strategy to study the interactions of the four compounds with tyrosinase and l-DOPA. The molecular docking result is consistent with that of the experiment. Finally, we selected RES + OXYR and used PIG1 cells to verify whether OXYR synergistically promotes RES activity on tyrosinase. The two agents had a synergistic inhibitory effect on tyrosinase activity. These results provided a novel synergistic strategy for antioxidants and tyrosinase inhibitors, and this strategy is useful in skin injury treatment.
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spelling pubmed-60170462018-11-13 Synergistic Promotion on Tyrosinase Inhibition by Antioxidants Wang, Yan Hao, Mi-Mi Sun, Ying Wang, Li-Feng Wang, Hao Zhang, Yan-Jun Li, Hong-Yan Zhuang, Peng-Wei Yang, Zhen Molecules Article When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocytes to produce melanin. Meanwhile, the Keap1-Nrf2/ARE pathway, which removes ROS, is activated at increased ROS levels, and antioxidant compounds facilitates the dissociation of Nrf2. In this study, we explored the possible suppressing effects of antioxidant compounds and tyrosine inhibitors on melanin formation and the promotory effects of these compounds on ROS scavenging. The antioxidant activity of glabridin (GLA), resveratrol (RES), oxyresveratrol (OXYR), and phenylethylresorcinol (PR) were investigated via the stable free radical 2,2-diphenyl-1-picrylhydrazyl method. The inhibitory effects of the four compounds and their mixtures on tyrosinase were evaluated. l-Tyrosine or 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA) was used as a substrate. The results showed that all mixtures did not exhibit synergistic effects with the l-tyrosine as a substrate, suggesting that l-tyrosine is not suitable as a substrate. However, the mixtures of “GLA:RES,” “GLA:OXYR,” “OXYR:RES,” and “PR:RES” demonstrated synergistic effects (CI < 0.9, p < 0.05), whereas “GLA:RES” and “PR:OXYR” indicated an additive effect (0.9 ditive1, p < 0.05). Furthermore, we used a molecular docking strategy to study the interactions of the four compounds with tyrosinase and l-DOPA. The molecular docking result is consistent with that of the experiment. Finally, we selected RES + OXYR and used PIG1 cells to verify whether OXYR synergistically promotes RES activity on tyrosinase. The two agents had a synergistic inhibitory effect on tyrosinase activity. These results provided a novel synergistic strategy for antioxidants and tyrosinase inhibitors, and this strategy is useful in skin injury treatment. MDPI 2018-01-04 /pmc/articles/PMC6017046/ /pubmed/29300356 http://dx.doi.org/10.3390/molecules23010106 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Yan
Hao, Mi-Mi
Sun, Ying
Wang, Li-Feng
Wang, Hao
Zhang, Yan-Jun
Li, Hong-Yan
Zhuang, Peng-Wei
Yang, Zhen
Synergistic Promotion on Tyrosinase Inhibition by Antioxidants
title Synergistic Promotion on Tyrosinase Inhibition by Antioxidants
title_full Synergistic Promotion on Tyrosinase Inhibition by Antioxidants
title_fullStr Synergistic Promotion on Tyrosinase Inhibition by Antioxidants
title_full_unstemmed Synergistic Promotion on Tyrosinase Inhibition by Antioxidants
title_short Synergistic Promotion on Tyrosinase Inhibition by Antioxidants
title_sort synergistic promotion on tyrosinase inhibition by antioxidants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017046/
https://www.ncbi.nlm.nih.gov/pubmed/29300356
http://dx.doi.org/10.3390/molecules23010106
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