{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:50:07Z","timestamp":1790913007542,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hyperpigmentation is a common acquired disorder that can be a cosmetic concern for many individuals. To reduce and prevent hyperpigmentation, numerous skin lightening agents have been developed. Potassium 4\u2010methoxysalicylate (4MSK) is a skin lightening agent that was approved as an active skin lightening ingredient of quasi\u2010drugs by the Ministry of Health, Labour and Welfare of Japan in 2003. For over 20\u2009years, 4MSK has been widely used in quasi\u2010drug and cosmetic products. However, the mechanism of action and efficacy of 4MSK on skin pigmentation and skin lightness have not been publicly reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to assess the mechanism of action and the efficacy of 4MSK on facial pigmentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mechanism of action of 4MSK on epidermal cells was investigated using human melanocytes, human keratinocytes, and human 3D epidermal equivalents. The efficacy of 4MSK on facial pigmentation was evaluated by a human clinical study, which is a double\u2010blind, split\u2010face, placebo\u2010controlled, paired\u2010design study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>4MSK significantly suppressed melanin content in cultured human melanocytes and a 3D epidermal equivalent. It also promoted gene expression of differentiation markers of human keratinocytes. In the clinical study, a 4MSK formulation significantly increased skin lightness values in both pigmented and non\u2010pigmented areas of cheek skin. In addition, it reduced the desquamation area ratio of the cheek.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>4MSK reduces skin pigmentation and contributes to brighter skin by acting on both melanocytes and keratinocytes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.70112","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T10:36:37Z","timestamp":1741775797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potassium 4\u2010Methoxysalicylate (<scp>4MSK<\/scp>) Exerts a Skin Lightening Effect by Acting on Melanocytes and Keratinocytes"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9268-5439","authenticated-orcid":false,"given":"Yutaka","family":"Shirasugi","sequence":"first","affiliation":[{"name":"MIRAI Technology Institute, Shiseido Co. Ltd.  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0830-5017","authenticated-orcid":false,"given":"Takako","family":"Shibata","sequence":"additional","affiliation":[{"name":"MIRAI Technology Institute, Shiseido Co. Ltd.  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saaya","family":"Koike","sequence":"additional","affiliation":[{"name":"MIRAI Technology Institute, Shiseido Co. Ltd.  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-1054","authenticated-orcid":false,"given":"Masao","family":"Hara","sequence":"additional","affiliation":[{"name":"MIRAI Technology Institute, Shiseido Co. Ltd.  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyotaka","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"MIRAI Technology Institute, Shiseido Co. Ltd.  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Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5964-2556","authenticated-orcid":false,"given":"Yoko","family":"Funasaka","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ikebukuro West Gate Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2016.1256882"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.14095"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms11062566"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27154774"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174458"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.67.631"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/np50106a021"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/znc-2007-3-412"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700066"},{"key":"e_1_2_11_11_1","first-page":"455","article-title":"Salicylic Acid as a Peeling Agent: A Comprehensive Review","volume":"8","author":"Alif T.","year":"2015","journal-title":"Clinical, Cosmetic and Investigational Dermatology"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(03)00071-4"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.7.4097"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.30.17702"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12472288"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90073-N"},{"key":"e_1_2_11_17_1","first-page":"609","article-title":"Inhibitory Effect of Arbutin on Melanogenesis\u2013Biochemical Study Using Cultured B16 Melanoma Cells","volume":"101","author":"Akiu S.","year":"1991","journal-title":"Nihon Hifuka Gakkai Zasshi"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)12357-4"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.2216"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1467-2494.2000.00023.x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094466"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2001.100105.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07830.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.07.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.136.11.1390"}],"updated-by":[{"DOI":"10.1111\/jocd.70317","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000}}],"container-title":["Journal of Cosmetic Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.70112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T18:57:46Z","timestamp":1744225066000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jocd.70112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/jocd.70112"],"URL":"https:\/\/doi.org\/10.1111\/jocd.70112","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1111\/jocd.70317","asserted-by":"object"}]},"ISSN":["1473-2130","1473-2165"],"issn-type":[{"value":"1473-2130","type":"print"},{"value":"1473-2165","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2025-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70112"}}