{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:46Z","timestamp":1792806166367,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pukyong National University Industry\u2013University Cooperation Research Fund","award":["202312160001"],"award-info":[{"award-number":["202312160001"]}],"id":[{"id":"https:\/\/ror.org\/0433kqc49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Ministry of Education","award":["NRF-2021R1A6A1A03039211"],"award-info":[{"award-number":["NRF-2021R1A6A1A03039211"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Ministry of Education","award":["NRF-2022R1C1C2005467"],"award-info":[{"award-number":["NRF-2022R1C1C2005467"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Melanogenesis, essential for skin photoprotection and pigmentation, can lead to disorders like melasma and hyperpigmentation, which are challenging to treat and affect quality of life. Docosatrienoic acid (DTA), a polyunsaturated omega-3 fatty acid, has been identified as a potential regulator of skin aging. This study investigates DTA\u2019s effects on melanogenesis and its underlying molecular mechanisms using in silico and in vitro analyses. SwissSimilarity analysis revealed that DTA shares close structural similarities with known anti-melanogenic lipids, suggesting it may inhibit melanogenesis in similar manners. Our results demonstrated that DTA reduces melanin content and intracellular tyrosinase activity in B16F10 cells, significantly downregulating the mRNA expression of tyrosinase, TRP-1, and TRP-2 by inhibiting MITF translocation to the nucleus. While DTA exhibited mild inhibitory effects on mushroom tyrosinase activity and antioxidant properties at higher concentrations, direct inhibition of tyrosinase is likely not the primary mechanism, as the observed anti-melanogenic effects occurred at much lower concentrations compared to those required for direct tyrosinase inhibition. Together, DTA-mediated modulation of MITF and tyrosinase mRNA expression offers a novel approach to treating hyperpigmentation. DTA\u2019s potential extends into the cosmetic industry, enhancing product stability, functionality, and aesthetics. Further research is needed to explore DTA\u2019s broader applications in skincare and cosmetic formulations.<\/jats:p>","DOI":"10.3390\/ph17091198","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T07:59:46Z","timestamp":1726041586000},"page":"1198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Docosatrienoic Acid Inhibits Melanogenesis Partly through Suppressing the Intracellular MITF\/Tyrosinase Axis"],"prefix":"10.3390","volume":"17","author":[{"given":"Kyoung","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-8743","authenticated-orcid":false,"given":"Min-Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Biotechnology Research Division, National Institute of Fisheries Science, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0789-5935","authenticated-orcid":false,"given":"Su-Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeseong","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5878-1201","authenticated-orcid":false,"given":"Ah-reum","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonggi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/pcmr.13165","article-title":"The metabolism of melanin synthesis\u2014From melanocytes to melanoma","volume":"37","author":"Snyman","year":"2024","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3892\/etm.2020.8687","article-title":"Natural skin-whitening compounds for the treatment of melanogenesis (Review)","volume":"20","author":"Qian","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/jdv.15987","article-title":"Psychological disturbances in patients with pigmentary disorders: A cross-sectional study","volume":"34","author":"Dabas","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.4103\/ijd.ijd_1067_21","article-title":"Melanogenesis and Hypopigmentation: The Case of Vitiligo","volume":"67","author":"Vinardell","year":"2022","journal-title":"Indian J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Slominski, R.M., Sarna, T., P\u0142onka, P.M., Raman, C., Bro\u017cyna, A.A., and Slominski, A.T. (2022). Melanoma, melanin, and melanogenesis: The Yin and Yang relationship. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.842496"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lee, M.K., Ryu, H., Lee, J.Y., Jeong, H.H., Baek, J., Van, J.Y., Kim, M.J., and Jung, W.K. (2022). Potential Beneficial Effects of Sargassum spp. in Skin Aging. Mar. Drugs, 20.","DOI":"10.3390\/md20080540"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cellsig.2017.09.004","article-title":"Recent development of signaling pathways inhibitors of melanogenesis","volume":"40","author":"Pillaiyar","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2308374121","DOI":"10.1073\/pnas.2308374121","article-title":"Photo-neuro-immuno-endocrinology: How the ultraviolet radiation regulates the body, brain, and immune system","volume":"121","author":"Slominski","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","unstructured":"Ahmad, M.U. (2017). Chapter 12\u2014The Role of Fatty Acids in Cosmetic Technology. Fatty Acids, AOCS Press."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s004030050320","article-title":"Linoleic acid and \u03b1-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin","volume":"290","author":"Ando","year":"1998","journal-title":"Arch. Dermatol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1194\/jlr.M090712","article-title":"Effect of fatty acids on melanogenesis and tumor cell growth in melanoma cells","volume":"60","author":"Yamada","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chocarro-Calvo, A., Jociles-Ortega, M., Garcia-Martinez, J.M., Louphrasitthiphol, P., Vivas-Garcia, Y., Ram\u00edrez-S\u00e1nchez, A., Chauhan, J., Fiuza, M.C., Duran, M., and Garc\u00eda-Jim\u00e9nez, C. (2024). Phenotype-specific melanoma uptake of fatty acid from human adipocytes activates AXL and CAV1-dependent beta-catenin nuclear accumulation. bioRxiv.","DOI":"10.1101\/2024.01.21.576568"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1034\/j.1600-0560.2003.300104.x","article-title":"Fatty acid synthase expression in melanoma","volume":"30","author":"Innocenzi","year":"2003","journal-title":"J. Cutan. Pathol."},{"key":"ref_14","first-page":"314","article-title":"Increase of melanogenesis in the presence of fatty acids","volume":"1","author":"Shabani","year":"2010","journal-title":"Pharmacologyonline"},{"key":"ref_15","first-page":"111","article-title":"The effect of docosatrienoic acid on the potassium channels of outward rectification in the membrane of rat peritoneal macrophages","volume":"81","author":"Krutetskaia","year":"1995","journal-title":"Fiziol. Zhurnal Im. I.M. Sechenova"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1080\/01635581.2020.1804949","article-title":"Comparing the in vitro antitumor, antioxidant and anti-inflammatory activities between two new very long chain polyunsaturated fatty acids, docosadienoic acid (DDA) and docosatrienoic acid (DTA), and docosahexaenoic acid (DHA)","volume":"73","author":"Chen","year":"2021","journal-title":"Nutr. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1021\/acs.jcim.6b00174","article-title":"SwissSimilarity: A Web Tool for Low to Ultra High Throughput Ligand-Based Virtual Screening","volume":"56","author":"Zoete","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/BF02536211","article-title":"Accumulation of (n-9)-eicosatrienoic and docosatrienoic acids in human fibroblast phospholipids","volume":"23","author":"Karmiol","year":"1988","journal-title":"Lipids"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.5650\/jos.59.315","article-title":"Effect of palmitoleic acid on melanogenic protein expression in murine b16 melanoma","volume":"59","author":"Yoon","year":"2010","journal-title":"J. Oleo Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mustonen, A.M., and Nieminen, P. (2023). Dihomo-\u03b3-Linolenic Acid (20:3n-6)-Metabolism, Derivatives, and Potential Significance in Chronic Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032116"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1042\/BJ20051419","article-title":"Intracellular composition of fatty acid affects the processing and function of tyrosinase through the ubiquitin\u2013proteasome pathway","volume":"394","author":"Ando","year":"2006","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Solano, F. (2020). Photoprotection and skin pigmentation: Melanin-related molecules and some other new agents obtained from natural sources. Molecules, 25.","DOI":"10.3390\/molecules25071537"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1073\/pnas.93.3.1087","article-title":"DNA damage enhances melanogenesis","volume":"93","author":"Eller","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3746\/pnf.2022.27.4.423","article-title":"Fish Collagen Peptide (Naticol\u00ae) Protects the Skin from Dryness, Wrinkle Formation, and Melanogenesis Both In Vitro and In Vivo","volume":"27","author":"Lee","year":"2022","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3746\/jfn.2010.15.3.213","article-title":"Antioxidant activities and melanogenesis inhibitory effects of Terminalia chebula in B16\/F10 melanoma cells","volume":"15","author":"Lee","year":"2010","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Panich, U. (2011). Antioxidant defense and UV-induced melanogenesis: Implications for melanoma prevention. Current Management of Malignant Melanoma, IntechOpen.","DOI":"10.5772\/18920"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Slipicevic, A., J\u00f8rgensen, K., Skrede, M., Rosnes, A.K.R., Tr\u00f8en, G., Davidson, B., and Fl\u00f8renes, V.A. (2008). The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells. BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-276"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, M.-K., Ryu, H., Jeong, H.H., and Lee, B. (2022). Brassinin abundant in Brassicaceae suppresses melanogenesis through dual mechanisms of tyrosinase inhibition. Foods, 12.","DOI":"10.3390\/foods12010121"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Moon, K.M., Yang, J.-H., Lee, M.-K., Kwon, E.-B., Baek, J., Hwang, T., Kim, J.-I., and Lee, B. (2022). Maclurin exhibits antioxidant and anti-tyrosinase activities, suppressing melanogenesis. Antioxidants, 11.","DOI":"10.3390\/antiox11061164"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.foodchem.2018.08.144","article-title":"Xanthone-related compounds as an anti-browning and antioxidant food additive","volume":"274","author":"Moon","year":"2019","journal-title":"Food Chem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:07:20Z","timestamp":1759133240000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,11]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ph17091198"],"URL":"https:\/\/doi.org\/10.3390\/ph17091198","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,11]]}}}