{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:21:02Z","timestamp":1789881662204,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T00:00:00Z","timestamp":1421020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Photochem &amp; Photobiology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nobiletin is a unique flavonoid having polymethoxy groups and has exhibited anti\u2010inflammatory and antiobesity effects. Here, we examined the inhibition of nobiletin on melanogenesis induced by endothelin\u20101 (ET) and stem cell factor (SCF) in normal human melanocytes. Nobiletin dose dependently reduced ET plus SCF\u2010stimulated tyrosinase activity without causing cytotoxicity. Nobiletin reduced cAMP\u2010response element\u2010binding protein (CREB) phosphorylation and microphthalmia\u2010associated transcription factor (MITF) expression, which is a key transcription factor for tyrosinase expression in pigmentation induced by ET plus SCF stimulation. Nobiletin treatment effectively decreased ET plus SCF\u2010induced Raf\u20101, MEK and ERK1\/2 phosphorylation and also downregulated the forskolin\u2010induced phosphorylation of CREB. Furthermore, nobiletin inhibited ET plus SCF\u2010triggered production of melanin and expression of MITF\/tyrosinase in a three\u2010dimensional human epidermal model. In accordance with protein expression, the expression of genes related to the pigmentation was also increased in the cells stimulated with ET plus SCF and the cotreatment with nobiletin decreased obviously the ET plus SCF\u2010triggered gene expressions of tyrosinase, PMEL, TRP1 and MITF. Nobiletin contributes to hypopigmentation by downregulating MITF and tyrosinase expression through reduced Raf\u20101 phosphorylation. Our findings implicate nobiletin as a potential new whitening agent.<\/jats:p>","DOI":"10.1111\/php.12400","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T16:04:20Z","timestamp":1418141060000},"page":"379-386","source":"Crossref","is-referenced-by-count":31,"title":["Nobiletin, a Polymethoxy Flavonoid, Reduced Endothelin\u20101 Plus SCF\u2010Induced Pigmentation in Human Melanocytes"],"prefix":"10.1111","volume":"91","author":[{"given":"Hyo Jung","family":"Kim","sequence":"first","affiliation":[{"name":"Research Institute for Biological Functions Chubu University Kasugai Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yonezawa","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Functions Chubu University Kasugai Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Teruya","sequence":"additional","affiliation":[{"name":"Faculty of Education University of the Ryukyus Nishihara Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je\u2010Tae","family":"Woo","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Functions Chubu University Kasugai Aichi Japan"},{"name":"Department of Research and Development Erina Co., Inc. Minato\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung\u2010Yoon","family":"Cha","sequence":"additional","affiliation":[{"name":"Research Institute for Biological Functions Chubu University Kasugai Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2003.00029.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"24675","DOI":"10.1016\/S0021-9258(18)35817-4","article-title":"Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocyte","volume":"267","author":"Imokawa G.","year":"1992","journal-title":"J. Biol. 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