{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:04:04Z","timestamp":1789664644033,"version":"4.0.1"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2022 Scientific Promotion Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hyperpigmentation is a common condition that causes darker spots or patches on the skin, which often look brown, black, gray, red, or pink. This results in unresolved psychological impact due to high anxiety, depression, and somatoform disorder. We aimed to repurpose an antidiabetic drug, miglitol, as an effective compound against hyperpigmentation when applied as a cosmeceutical agent. The present study investigated the antimelanogenic effects of miglitol and the trehalase inhibitor validamycin A. Miglitol in isolation exhibited no cytotoxicity and significantly reduced the melanin production and intracellular tyrosinase activity in B16F10 melanoma cells. The Western blotting results showed that miglitol reduces the expression of melanogenic regulatory factors, including tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF). Mechanistically, miglitol appears to suppress melanin synthesis through cAMP-dependent protein kinase (PKA)-dependent downregulation of MITF, a master transcription factor in melanogenesis. The antimelanogenic effects of miglitol was mediated by downregulation of the p38 signaling pathway and upregulation of extracellular signal-regulated kinase (ERK). Moreover, miglitol decreases P-GSK3\u03b2 and \u03b2-catenin levels compared to those in the untreated group. However, miglitol activated P-\u03b2-catenin expression compared to that in the untreated group. Finally, we tested the potential of miglitol in topical application through primary human skin irritation tests on the normal skin (upper back) of 33 volunteers. In these assays, miglitol (125 and 250 \u03bcM) did not induce any adverse reactions. Taken together, these findings suggest that the regulation of melanogenesis by miglitol may be mediated by the PKA, MAPK, and GSK3\u03b2\/\u03b2-Catenin signaling pathways and that miglitol might provide new insights into drug repurposing for the treatment of hyperpigmentation symptoms.<\/jats:p>","DOI":"10.3390\/molecules28010115","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T02:50:01Z","timestamp":1672109401000},"page":"115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Miglitol, an Oral Antidiabetic Drug, Downregulates Melanogenesis in B16F10 Melanoma Cells through the PKA, MAPK, and GSK3\u03b2\/\u03b2-Catenin Signaling Pathways"],"prefix":"10.3390","volume":"28","author":[{"given":"Hyeon-Mi","family":"Kim","sequence":"first","affiliation":[{"name":"Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3000-7989","authenticated-orcid":false,"given":"Chang-Gu","family":"Hyun","sequence":"additional","affiliation":[{"name":"Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.2174\/1871520622666220317140557","article-title":"Drug Repurposing Strategies for Non-cancer to Cancer Therapeutics","volume":"22","author":"Singhal","year":"2022","journal-title":"Anti-Cancer Agents Med. 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