{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:34:34Z","timestamp":1788518074488,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Biological Resources (NIBR) of the Ministry of Environment (MOE) of the Republic of Korea","award":["NIBR202203112"],"award-info":[{"award-number":["NIBR202203112"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Dimethyl itaconate (DMI) exhibits an anti-inflammatory effect. Activation of nuclear factor erythroid 2-related factor 2 (NRF2) is implicated in the inhibition of melanogenesis. Therefore, DMI and itaconic acid (ITA), classified as NRF2 activators, have potential uses in hyperpigmentation reduction. The activity of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), an important transcription factor for MITF gene promoter, is regulated by glycogen synthase kinase 3\u03b2 (GSK3\u03b2) and protein kinase A (PKA). Here, we investigated the inhibitory effect of ITA and DMI on alpha-melanocyte-stimulating hormone (\u03b1-MSH)-induced MITF expression and the modulatory role of protein kinase B (AKT) and GSK3\u03b2 in melanogenesis in B16F10 mouse melanoma cells. These cells were incubated with \u03b1-MSH alone or in combination with ITA or DMI. Proteins were visualized and quantified using immunoblotting and densitometry. Compared to ITA, DMI treatment exhibited a better inhibitory effect on the \u03b1-MSH-induced expression of melanogenic proteins such as MITF. Our data indicate that DMI exerts its anti-melanogenic effect via modulation of the p38 mitogen-activated protein kinase (MAPK) and AKT signaling pathways. In conclusion, DMI may be an effective therapeutic agent for both inflammation and hyperpigmentation.<\/jats:p>","DOI":"10.3390\/molecules27134183","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T22:43:28Z","timestamp":1656542608000},"page":"4183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dimethyl Itaconate Reduces \u03b1-MSH-Induced Pigmentation via Modulation of AKT and p38 MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-4080","authenticated-orcid":false,"given":"Sungchan","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, Asan 31460, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Jae","family":"Chi","sequence":"additional","affiliation":[{"name":"Microorganism Resources Division, National Institute of Biological Resources, Incheon 17058, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, Asan 31460, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3109\/17453054.2010.525439","article-title":"The skin is the body\u2019s largerst organ","volume":"33","author":"Swann","year":"2010","journal-title":"J. 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