{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:05:39Z","timestamp":1791903939441,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"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":["NRF-2018R1C1B6007728"],"award-info":[{"award-number":["NRF-2018R1C1B6007728"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1C1C1006516"],"award-info":[{"award-number":["NRF-2021R1C1C1006516"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, effectively stimulated melanogenesis. Treatment of B16-F10 cells with fraxinol increased the melanin content and tyrosinase activity in a concentration-dependent manner without causing cytotoxicity. Additionally, fraxinol enhanced the mRNA expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Fraxinol also increased the expression of microphthalmia-associated transcription factor at both mRNA and protein levels. Fraxinol upregulated the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). Furthermore, H89, a cAMP\u2013dependent protein kinase A inhibitor, decreased fraxinol-induced CREB phosphorylation and microphthalmia-associated transcription factor expression and significantly attenuated the fraxinol-induced melanin content and intracellular tyrosinase activity. These results suggest that fraxinol enhances melanogenesis via a protein kinase A-mediated mechanism, which may be useful for developing potent melanogenesis stimulators.<\/jats:p>","DOI":"10.3390\/molecules27051549","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:48:33Z","timestamp":1645994913000},"page":"1549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Fraxinol Stimulates Melanogenesis in B16F10 Mouse Melanoma Cells through CREB\/MITF Signaling"],"prefix":"10.3390","volume":"27","author":[{"given":"Sun Young","family":"Moon","sequence":"first","affiliation":[{"name":"Division of Applied Life Science (BK21), PMBBRC and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi-Marjahan","family":"Akter","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-0746","authenticated-orcid":false,"given":"Mi-Jeong","family":"Ahn","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-3415","authenticated-orcid":false,"given":"Kwang Dong","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Applied Life Science (BK21), PMBBRC and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Applied Life Science (BK21), PMBBRC and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4921-0909","authenticated-orcid":false,"given":"Joon-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Animal Bioscience, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-1645","authenticated-orcid":false,"given":"Jeong-Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (BK21), College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6505-3080","authenticated-orcid":false,"given":"Cheol","family":"Hwangbo","sequence":"additional","affiliation":[{"name":"Division of Applied Life Science (BK21), PMBBRC and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.24625.1","article-title":"Recent advances in understanding the molecular basis of melanogenesis in melanocytes","volume":"9","author":"Ohbayashi","year":"2020","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nature05660","article-title":"Melanocyte biology and skin pigmentation","volume":"445","author":"Lin","year":"2007","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1586\/edm.10.70","article-title":"Update on the regulation of mammalian melanocyte function and skin pigmentation","volume":"6","author":"Kondo","year":"2011","journal-title":"Expert Rev. 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