{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:17:46Z","timestamp":1760239066585,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1F1A1049980","2018R1A6A1A03025124"],"award-info":[{"award-number":["2020R1F1A1049980","2018R1A6A1A03025124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Melanin protects skin from ultraviolet radiation, toxic drugs, and chemicals. Its synthesis is sophisticatedly regulated by multiple mechanisms, including transcriptional and enzymatic controls. However, uncontrolled excessive production of melanin can cause serious dermatological disorders, such as freckles, melasma, solar lentigo, and cancer. Moreover, melanogenesis disorders are also linked to neurodegenerative diseases. Therefore, there is a huge demand for safer and more potent inhibitors of melanogenesis. In the present study, we report novel inhibitory effects of Jeju magma-seawater (JMS) on melanogenesis induced by \u03b1-melanocyte stimulating hormone (\u03b1-MSH) in B16F10 melanoma cells. JMS is the abundant underground seawater found in Jeju Island, a volcanic island of Korea. Research into the physiological effects of JMS is rapidly increasing due to its high contents of various minerals that are essential to human health. However, little is known about the effects of JMS on melanogenesis. Here, we demonstrate that JMS safely and effectively inhibits \u03b1-MSH-induced melanogenesis via the CaMKK\u03b2 (calcium\/calmodulin-dependent protein kinase \u03b2)-AMPK (5\u2032 adenosine monophosphate-activated protein kinase) signaling pathway. We further demonstrate that AMPK inhibits the signaling pathways of protein kinase A and MAPKs (mitogen-activated protein kinase), which are critical for melanogenesis-related gene expression. Our results highlight the potential of JMS as a novel therapeutic agent for ameliorating skin pigmentation-related disorders.<\/jats:p>","DOI":"10.3390\/md18090473","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T10:22:23Z","timestamp":1600424543000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Jeju Magma-Seawater Inhibits \u03b1-MSH-Induced Melanogenesis via CaMKK\u03b2-AMPK Signaling Pathways in B16F10 Melanoma Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Minhyeok","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Easy Hydrogen Corporation, Jeju City 63196, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5580-4338","authenticated-orcid":false,"given":"Young-Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, Jeju National University, Jeju City 63196, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dang Hieu","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-9482","authenticated-orcid":false,"given":"Wonchae","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-1008","authenticated-orcid":false,"given":"Insug","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joohun","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","article-title":"The protective role of melanin against uv damage in human skin","volume":"84","author":"Brenner","year":"2008","journal-title":"Photochem. 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