{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:15:17Z","timestamp":1774314917596,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skin hyperpigmentation is generally characterized by increased synthesis and deposition of melanin in the skin. UP256, containing bakuchiol, is a well-known medication for acne vulgaris. Acne sometimes leaves dark spots on the skin, and we hypothesized that UP256 may be effective against hyperpigmentation-associated diseases. UP256 was treated for anti-melanogenesis and melanocyte dendrite formation in cultured normal human epidermal melanocytes as well as in the reconstituted skin and zebrafish models. Western blot analysis and glutathione S-transferase (GST)-pull down assays were used to evaluate the expression and interaction of enzymes related in melanin synthesis and transportation. The cellular tyrosinase activity and melanin content assay revealed that UP256 decreased melanin synthesis by regulating the expression of proteins related on melanogenesis including tyrosinase, TRP-1 and -2, and SOX9. UP256 also decreased dendrite formation in melanocytes via regulating the Rac\/Cdc42\/\u03b1-PAK signaling proteins, without cytotoxic effects. UP256 also inhibited ciliogenesis-dependent melanogenesis in normal human epidermal melanocytes. Furthermore, UP256 suppressed melanin contents in the zebrafish and the 3D human skin tissue model. All things taken together, UP256 inhibits melanin synthesis, dendrite formation, and primary cilium formation leading to the inhibition of melanogenesis.<\/jats:p>","DOI":"10.3390\/ijms21155341","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T10:16:49Z","timestamp":1595931409000},"page":"5341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["UP256 Inhibits Hyperpigmentation by Tyrosinase \r\nExpression\/Dendrite Formation via Rho-Dependent \r\nSignaling and by Primary Cilium Formation \r\nin Melanocytes"],"prefix":"10.3390","volume":"21","author":[{"given":"Min Cheol","family":"Kang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Gachon University 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Wook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taek Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei University, Songdo-dong, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4851-7650","authenticated-orcid":false,"given":"Lalita","family":"Subedi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-4978","authenticated-orcid":false,"given":"Hussain M.","family":"Wahedi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Medical Sciences, Mall Road, Rawalpindi 46000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon-Gil","family":"Do","sequence":"additional","affiliation":[{"name":"Wellness R&amp;D Center, Univera, Inc., Seoul 04782, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-1732","authenticated-orcid":false,"given":"Eunju","family":"Shin","sequence":"additional","affiliation":[{"name":"Wellness R&amp;D Center, Univera, Inc., Seoul 04782, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Yi","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-5613","authenticated-orcid":false,"given":"Sun Yeou","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea"},{"name":"Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1111\/jocd.12747","article-title":"The role of systemic treatments for skin lightening","volume":"17","author":"Juhasz","year":"2018","journal-title":"J. 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