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Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis

Ziziphus jujuba extracts possess a broad spectrum of biological activities, such as antioxidant and anticancer activities in melanoma cancers. Nevertheless, the compounds contain high antioxidant capacities and anticancer activities in melanoma cells, shown to be effective in hyperpigmentation disor...

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Autores principales: Molagoda, Ilandarage Menu Neelaka, Lee, Kyoung-Tae, Athapaththu, Athapaththu Mudiyanselage Gihan Kavinda, Choi, Yung-Hyun, Hwang, Jaeyoung, Sim, Su-Jin, Kang, Sanghyuck, Kim, Gi-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304508/
https://www.ncbi.nlm.nih.gov/pubmed/34299326
http://dx.doi.org/10.3390/ijms22147701
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author Molagoda, Ilandarage Menu Neelaka
Lee, Kyoung-Tae
Athapaththu, Athapaththu Mudiyanselage Gihan Kavinda
Choi, Yung-Hyun
Hwang, Jaeyoung
Sim, Su-Jin
Kang, Sanghyuck
Kim, Gi-Young
author_facet Molagoda, Ilandarage Menu Neelaka
Lee, Kyoung-Tae
Athapaththu, Athapaththu Mudiyanselage Gihan Kavinda
Choi, Yung-Hyun
Hwang, Jaeyoung
Sim, Su-Jin
Kang, Sanghyuck
Kim, Gi-Young
author_sort Molagoda, Ilandarage Menu Neelaka
collection PubMed
description Ziziphus jujuba extracts possess a broad spectrum of biological activities, such as antioxidant and anticancer activities in melanoma cancers. Nevertheless, the compounds contain high antioxidant capacities and anticancer activities in melanoma cells, shown to be effective in hyperpigmentation disorders, but whether flavonoid glycosides from Z. jujuba regulate anti-melanogenesis remains unclear. In this study, we evaluated the anti-melanogenic activity of five flavonoid glycosides from Z. jujuba var. inermis (Bunge) Rehder seeds, including jujuboside A (JUA), jujuboside B (JUB), epiceanothic acid (EPA), betulin (BTL), and 6’’’-feruloylspinosin (FRS), in B16F10 melanoma cells and zebrafish larvae. According to our results, JUB, EPA, and FRS potently inhibited α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and prevented hyperpigmentation in zebrafish larvae. In particular, under α-MSH-stimulated conditions, FRS most significantly inhibited α-MSH-induced intracellular and extracellular melanin content in B16F10 melanoma cells. Additionally, JUB, EPS, and FRS remarkably downregulated melanogenesis in α-MSH-treated zebrafish larvae, with no significant change in heart rate. Neither JUA nor BTA were effective in downregulating melanogenesis in B16F10 melanoma cells and zebrafish larvae. Furthermore, JUB, EPA, and FRS directly inhibited in vitro mushroom tyrosinase enzyme activity. JUB, EPA, and FRS also downregulated cyclic adenosine monophosphate (cAMP) levels and the phosphorylation of cAMP-response element-binding protein (CREB), and subsequent microphthalmia transcription factor (MITF) and tyrosinase expression. In conclusion, this study demonstrated that JUB, EPA, and FRS isolated from Z. jujuba var. inermis (Bunge) Rehder seeds exhibit potent anti-melanogenic properties by inhibition of the cAMP-CERB-MITF axis and consequent tyrosinase activity.
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spelling pubmed-83045082021-07-25 Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis Molagoda, Ilandarage Menu Neelaka Lee, Kyoung-Tae Athapaththu, Athapaththu Mudiyanselage Gihan Kavinda Choi, Yung-Hyun Hwang, Jaeyoung Sim, Su-Jin Kang, Sanghyuck Kim, Gi-Young Int J Mol Sci Article Ziziphus jujuba extracts possess a broad spectrum of biological activities, such as antioxidant and anticancer activities in melanoma cancers. Nevertheless, the compounds contain high antioxidant capacities and anticancer activities in melanoma cells, shown to be effective in hyperpigmentation disorders, but whether flavonoid glycosides from Z. jujuba regulate anti-melanogenesis remains unclear. In this study, we evaluated the anti-melanogenic activity of five flavonoid glycosides from Z. jujuba var. inermis (Bunge) Rehder seeds, including jujuboside A (JUA), jujuboside B (JUB), epiceanothic acid (EPA), betulin (BTL), and 6’’’-feruloylspinosin (FRS), in B16F10 melanoma cells and zebrafish larvae. According to our results, JUB, EPA, and FRS potently inhibited α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and prevented hyperpigmentation in zebrafish larvae. In particular, under α-MSH-stimulated conditions, FRS most significantly inhibited α-MSH-induced intracellular and extracellular melanin content in B16F10 melanoma cells. Additionally, JUB, EPS, and FRS remarkably downregulated melanogenesis in α-MSH-treated zebrafish larvae, with no significant change in heart rate. Neither JUA nor BTA were effective in downregulating melanogenesis in B16F10 melanoma cells and zebrafish larvae. Furthermore, JUB, EPA, and FRS directly inhibited in vitro mushroom tyrosinase enzyme activity. JUB, EPA, and FRS also downregulated cyclic adenosine monophosphate (cAMP) levels and the phosphorylation of cAMP-response element-binding protein (CREB), and subsequent microphthalmia transcription factor (MITF) and tyrosinase expression. In conclusion, this study demonstrated that JUB, EPA, and FRS isolated from Z. jujuba var. inermis (Bunge) Rehder seeds exhibit potent anti-melanogenic properties by inhibition of the cAMP-CERB-MITF axis and consequent tyrosinase activity. MDPI 2021-07-19 /pmc/articles/PMC8304508/ /pubmed/34299326 http://dx.doi.org/10.3390/ijms22147701 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Molagoda, Ilandarage Menu Neelaka
Lee, Kyoung-Tae
Athapaththu, Athapaththu Mudiyanselage Gihan Kavinda
Choi, Yung-Hyun
Hwang, Jaeyoung
Sim, Su-Jin
Kang, Sanghyuck
Kim, Gi-Young
Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis
title Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis
title_full Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis
title_fullStr Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis
title_full_unstemmed Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis
title_short Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis
title_sort flavonoid glycosides from ziziphus jujuba var. inermis (bunge) rehder seeds inhibit α-melanocyte-stimulating hormone-mediated melanogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304508/
https://www.ncbi.nlm.nih.gov/pubmed/34299326
http://dx.doi.org/10.3390/ijms22147701
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