{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:24:21Z","timestamp":1791228261595,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Melanin overexpression causes skin hyperpigmentation, which is associated with various skin disorders and cosmetic concerns. Umbelliferone, a natural coumarin found widely in plant species, has been noted for its antioxidant and anti-inflammatory effects but has received little attention for its impact on melanogenesis. Here, the effects of umbelliferone on melanogenesis were investigated in vitro and in clinical studies. The results showed that umbelliferone was non-cytotoxic to human skin and B16F10 melanoma cells. It also exhibited significant anti-melanogenic effects, reducing both melanin production and tyrosinase activity in a dose-dependent manner. This effect was achieved through a decrease in tyrosinase mRNA levels. Furthermore, umbelliferone in a formulation was stable under different temperature conditions, and after four weeks of topical application, it significantly decreased the melanin index and increased skin lightness (L*) values compared to those at the baseline. Overall, these findings demonstrate the potential of umbelliferone as a promising skin-lightening agent in the cosmetics industry.<\/jats:p>","DOI":"10.3390\/molecules29235571","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:02:18Z","timestamp":1732593738000},"page":"5571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anti-Melanogenic Effects of Umbelliferone: In Vitro and Clinical Studies"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-5965","authenticated-orcid":false,"given":"Da Jung","family":"Kim","sequence":"first","affiliation":[{"name":"Skin Science Research Center, NewLife BST Co., Ltd., Seoul 08594, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4915-0817","authenticated-orcid":false,"given":"Min Sook","family":"Jung","sequence":"additional","affiliation":[{"name":"Skin Science Research Center, NewLife BST Co., Ltd., Seoul 08594, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Un","family":"Jin","sequence":"additional","affiliation":[{"name":"Skin Science Research Center, NewLife BST Co., Ltd., Seoul 08594, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1012-319X","authenticated-orcid":false,"given":"Mi Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Skin Science Research Center, NewLife BST Co., Ltd., Seoul 08594, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae Eun","family":"An","sequence":"additional","affiliation":[{"name":"Skin Science Research Center, NewLife BST Co., Ltd., Seoul 08594, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"de Szalay, S., and Wertz, P.W. (2023). Protective Barriers Provided by the Epidermis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043145"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Moreiras, H., Seabra, M.C., and Barral, D.C. (2021). Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202104.0441.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/lipd.12266","article-title":"Borage Oil Treated with Immobilized Lipase Inhibits Melanogenesis","volume":"55","author":"Shin","year":"2020","journal-title":"Lipids"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Han, H., and Hyun, C. (2023). Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040604"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"El-Nashar, H.A.S., El-Din, M.I.G., Hritcu, L., and Eldahshan, O.A. (2021). Insights on the Inhibitory Power of Flavonoids on Tyrosinase Activity: A Survey from 2016 to 2021. Molecules, 26.","DOI":"10.3390\/molecules26247546"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hushcha, Y., Blo, I., Oton-Gonzalez, L., Mauro, G.D., Martini, F., Tognon, M., and Mattei, M.D. (2021). MicroRNAs in the Regulation of Melanogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116104"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6328767","DOI":"10.1155\/2021\/6328767","article-title":"Camellia japonica Essential Oil Inhibits Alpha-MSH-induced Melanin Production and Tyrosinase activity in B16F10 Melanoma Cells","volume":"2021","author":"Ha","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/14756366.2016.1256882","article-title":"Skin Whitening Agents: Medicinal Chemistry Perspective of Tyrosinase Inhibitors","volume":"32","author":"Pillaiyar","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.bbagen.2012.05.003","article-title":"Potent Low Toxicity Inhibition of Human Melanogenesis by Novel Indole-Containing Octapeptides","volume":"1820","author":"Ubeid","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11373-006-9130-6","article-title":"Toxicogenomics of A375 Human Malignant Melanoma Cells Treated with Arbutin","volume":"14","author":"Cheng","year":"2007","journal-title":"J. Biomed. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6492346","DOI":"10.1155\/2021\/6492346","article-title":"Natural Coumarins: Exploring the Pharmacological Complexity and Underlying Molecular Mechanisms","volume":"2021","author":"Lopez","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s00706-018-2188-9","article-title":"Umbelliferone Instability During an Analysis Involving Its Extraction Process","volume":"149","author":"Dawidowicz","year":"2018","journal-title":"Monatsh. Chem."},{"key":"ref_13","unstructured":"Kesharwani, S., Patel, D.K., and Kesharwani, R. (2022). Bioactive-Loaded Nanomedicine for the Management of Health and Disease, Apple Academic Press. [1st ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kornicka, A., Balewski, \u0141., Lahutta, M., and Kokoszka, J. (2023). Umbelliferone and Its Synthetic Derivatives as Suitable Molecules for the Development of Agents With Biological Activities: A Review of Their Pharmacological and Therapeutic Potential. Pharmaceuticals, 16.","DOI":"10.3390\/ph16121732"},{"key":"ref_15","first-page":"223","article-title":"Umbelliferone: Sources, Chemistry and Bioactivities Review","volume":"55","author":"Mazimba","year":"2017","journal-title":"Bull. Fac. Pharm. Cairo Univ."},{"key":"ref_16","first-page":"59","article-title":"Bioactive Umbelliferone and Its Derivatives: An Update","volume":"8","author":"Radha","year":"2019","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s10787-023-01256-3","article-title":"Umbelliferon: A Review of Its Pharmacology, Toxicity and Pharmacokinetics","volume":"31","author":"Lin","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105694","DOI":"10.1016\/j.tiv.2023.105694","article-title":"Anticancer Effect of Umbelliferone on MKN-45 and MIA PaCa-2 Cell Lines","volume":"93","year":"2023","journal-title":"Toxicol. Vitr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105830","DOI":"10.1016\/j.intimp.2019.105830","article-title":"Umbelliferone Reduces the Expression of Inflammatory Chemokines in HaCaT Cells and DNCB\/DFE-Induced Atopic Dermatitis Symptoms in Mice","volume":"75","author":"Lim","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"PlCruz, L.F., de Figueiredo, G.F., Pedro, L.P., Amorin, Y.M., Andrade, J.T., Passos, T.F., Rodrigues, F.F., Souza, I.L.A.R., Gon\u00e7alves, T.P.R., and Dos Santos Lima, L.A.R. (2020). Umbelliferone (7-Hydroxycoumarin): A Non-toxic Antidiarrheal and Antiulcerogenic Coumarin. Biomed. Pharmacother., 129.","DOI":"10.1016\/j.biopha.2020.110432"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.jnutbio.2015.08.001","article-title":"The Complexity of the Nrf2 Pathway: Beyond the Antioxidant Response","volume":"26","author":"Huang","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kim, K., Huh, Y., and Lim, K.-M. (2021). Anti-pigmentary Natural Compounds and Their Mode of Action. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126206"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1080\/14786419.2020.1849200","article-title":"The Effect of Emodin on Melanogenesis Through The Modulation of ERK and MITF Signaling Pathway","volume":"36","author":"Kim","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Brown, A.D., Lynch, K., and Langelaan, D.N. (2023). The C-terminal Transactivation Domain of MITF Interacts Promiscuously with Co-activator CBP\/p300. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-43207-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1158\/0008-5472.CAN-18-2331","article-title":"MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma","volume":"79","author":"Kim","year":"2019","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gelmi, M.C., Houtzagers, L.E., Strub, T., Krossa, I., and Jager, M.J. (2022). MITF in Normal Melanocytes, Cutaneous and Uveal Melanoma: A Delicate Balance. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116001"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Guo, Y., Wu, W., and Yang, X. (2023). Coordinated MicroRNA\/mRNA Expression Profiles Reveal Unique Skin Color Regulatory Mechanisms in Chinese Giant Salamander (Andrias davidianus). Animals, 13.","DOI":"10.3390\/ani13071181"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1073\/pnas.92.5.1789","article-title":"Mitogenic and Melanogenic Stimulation of Normal Human Melanocytes by Melanotropic Peptides","volume":"92","author":"Swope","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.5483\/BMBRep.2010.43.7.461","article-title":"Inhibitory Effect of Glyceollin Isolated from Soybean Against Melanogenesis in B16 Melanoma Cells","volume":"43","author":"Lee","year":"2010","journal-title":"BMB Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chu, L.L., Pandey, R.P., Lim, H.N., Jung, H.J., Thuan, N.H., Kim, T.-S., and Sohng, J.K. (2017). Synthesis of Umbelliferone Derivatives in Escherichia coli and Their Biological Activities. J. Biol. Eng., 11.","DOI":"10.1186\/s13036-017-0056-5"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0378-8741(99)00165-8","article-title":"Antinociceptive, Anti-inflammatory and Bronchodilator Activities of Brazilian Medicinal Plants Containing Coumarin: A Comparative Study","volume":"70","author":"Leal","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/(SICI)1099-1573(199705)11:3<211::AID-PTR72>3.0.CO;2-W","article-title":"Analgesic and Antiinflammatory Activities of Justicia pectoralis Jacq and Its Main Constituents: Coumarin and Umbelliferone","volume":"11","author":"Lino","year":"1997","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Matos, M.J. (2021). Coumarin and Its Derivatives. Molecules, 26.","DOI":"10.3390\/molecules26206320"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lin, J.T., Lalevee, J., and Cheng, D.C. (2022). Efficacy Analysis of New Copper Complex for Visible Light (455, 530 nm) Radical\/Cationic Photopolymerization: The Synergic Effects and Catalytic Cycle. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0270679"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Asgari, M., Memarian, H.R., and Sabzyan, H. (2022). Electron-transfer Induced Photo-oxidation of 4, 5-Dihydro-1, 2, 4-Oxadiazoles: Experimental and Computational Studies. J. Photochem. Photobiol. A, 432.","DOI":"10.1016\/j.jphotochem.2022.114032"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8135608","DOI":"10.1155\/2016\/8135608","article-title":"Photostability and Photostabilization of Drugs and Drug Products","volume":"2016","author":"Ahmad","year":"2016","journal-title":"Int. J. Photoenergy"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Arsalan, A., Qadeer, K., Ali, S.A., Ahmed, S., and Khan, R.A. (2020). The Effect of Albumin in Photostabilization of Riboflavin: A Kinetic Study. J. Photochem. Photobiol. A, 394.","DOI":"10.1016\/j.jphotochem.2020.112456"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1039\/D0BM00810A","article-title":"A Thermosensitive Nanoplatform for Photoacoustic Imaging and NIR Light Triggered Chemo-photothermal Therapy","volume":"8","author":"Chen","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_39","first-page":"233","article-title":"Vitamin A Palmitate Photostability and Stability over Time","volume":"55","author":"Carlotti","year":"2004","journal-title":"J. Cosmet. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4314\/tjpr.v10i3.5","article-title":"Evaluation of the Photostability and Photodynamic Efficacy of Rose Bengal Loaded in Multivesicular Liposomes","volume":"10","author":"Fadel","year":"2011","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_41","unstructured":"Connors, K.A., Amidon, G.L., and Stella, V.J. (1986). Chemical Stability of Pharmaceuticals. The Handbook for Pharmacists, John Wiley & Sons. [2nd ed.]."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tonnesen, H.H. (2004). Photostability of Drugs and Drug Formulations, CRC Press. [2nd ed.].","DOI":"10.1201\/9780367801021"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Alam, M.B., Bajpai, V.K., Lee, J., Zhao, P., Byeon, J.-H., Ra, J.-S., Majumder, R., Lee, J.S., Yoon, J.-I., and Rather, I.A. (2017). Inhibition of Melanogenesis by Jineol from Scolopendra subspinipes mutilans via MAP-Kinase Mediated MITF Downregulation and the Proteasomal Degradation of Tyrosinase. Sci. Rep., 7.","DOI":"10.1038\/srep45858"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/23\/5571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:39:20Z","timestamp":1760114360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/23\/5571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":43,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["molecules29235571"],"URL":"https:\/\/doi.org\/10.3390\/molecules29235571","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]}}}