{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:50Z","timestamp":1772755250911,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T00:00:00Z","timestamp":1405641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029, exhibits potent antimelanogenic activity. We isolated and purified an active metabolite and identified it as S-(\u2212)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin synthesis, we first measured the size of the melanin biosynthesis inhibition zone caused by dhFAME. dhFAME also showed inhibitory activity against mushroom tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition activity was also confirmed by zymography. In addition, we showed that dhFAME strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse-transcription polymerase chain reaction and showed that treatment of Melan-a cells with 35 \u03bcM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together, these results indicate  that dhFAME is a potent inhibitor of melanin synthesis that can potentially be used for cosmetic biomaterial(s).<\/jats:p>","DOI":"10.3390\/ijms150712750","type":"journal-article","created":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T10:30:52Z","timestamp":1405679452000},"page":"12750-12763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["S-(\u2212)-10,11-Dihydroxyfarnesoic Acid Methyl Ester Inhibits Melanin Synthesis in Murine Melanocyte Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Seung-Hwa","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Food Science & Biotechnology, Graduate School, Kyungpook National University, Daegu 702-701, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Won","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Nano-Science & Technology, Graduate School, Kyungpook National University, Daegu 702-701, Korea"},{"name":"Nano Convergence Practical Application Center, Daegu 704-801, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Hee","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biology, National Academy of Agricultural Science,  Rural Administration Agency, Suwon 441-707, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol-Sik","family":"Yoon","sequence":"additional","affiliation":[{"name":"Mycoplus Co., Ltd., Anyang 431-080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Cheon","family":"Shin","sequence":"additional","affiliation":[{"name":"Pohang Center for Evaluation of Biomaterials, Pohang Technopark, Pohang 790-834, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-7315","authenticated-orcid":false,"given":"Sang-Han","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food Science & Biotechnology, Graduate School, Kyungpook National University, Daegu 702-701, Korea"},{"name":"Department of Nano-Science & Technology, Graduate School, Kyungpook National University, Daegu 702-701, Korea"},{"name":"Food & Bio-Industry Research Institute, Kyungpook National University, Daegu 702-701, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1600-0749.1995.tb00663.x","article-title":"New thioureas and related substances intended for melanoma targeting","volume":"8","author":"Larsson","year":"1995","journal-title":"Pigment. Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.3390\/ijms10125326","article-title":"The hunt for natural skin whitening agents","volume":"10","author":"Smit","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.3390\/ijms11062566","article-title":"Quasi-drugs developed in Japan for the prevention or treatment of hyperpigmentary disorders","volume":"11","author":"Ando","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2165\/11536930-000000000-00000","article-title":"Postinflammatory hyperpigmentation: Etiologic and therapeutic considerations","volume":"12","author":"Callender","year":"2011","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E8","DOI":"10.1038\/skinbio.2011.4","article-title":"Determination of melanin synthetic pathways","volume":"131","author":"Hearing","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.mrfmmm.2004.11.015","article-title":"Cellular and molecular events leading to the development of skin cancer","volume":"571","author":"Melnikova","year":"2005","journal-title":"Mutat. Res."},{"key":"ref_7","unstructured":"Nam, S.H., Yoon, C.S., Jeon, J.Y, Lee, S.H., Lee, K.G., Yeo, J.H., and Hwang, J.S. (2013). Mass Producing Method Of S-(\u2212)-10,11-Dihydroxyfarnesoic Acid Methyl Ester For Suppressing Agent Of Melanogenesis. (#10-1258699), Korea Patent."},{"key":"ref_8","unstructured":"Nam, S.H., Yoon, C.S., Jeon, J.Y., Lee, S.H., Lee, K.G., Yeo, J.H., and Hwang, J.S. (2013). Composition for Suppressing Production of Melanogenesis. (#10-1239631), Korea Patent."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3109\/15569527.2012.684419","article-title":"Postinflammatory hyperpigmentation secondary to external insult: An overview of the quantitative analysis of pigmentation","volume":"32","author":"Lamel","year":"2013","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nature05660","article-title":"Melanocytebiology and skin pigmentation","volume":"445","author":"Lin","year":"2007","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1365-2230.2010.03916.x","article-title":"Antioxidants add protection to a broad-spectrum sunscreen","volume":"36","author":"Wu","year":"2011","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_12","first-page":"1079","article-title":"Insect juvenile hormone analogues","volume":"40","year":"2011","journal-title":"Annu. Rev. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jinsphys.2006.03.004","article-title":"Role of juvenile hormone esterase and epoxide hydrolase in reproduction of the cotton bollworm, Helicoverpa zea","volume":"52","author":"Khalil","year":"2006","journal-title":"J. Insect. Physiol."},{"key":"ref_14","first-page":"134","article-title":"Inhibitory action of kojic acid on melanogenesis and its therapeutic effect for various human hyper-pigmentation disorders","volume":"36","author":"Mishima","year":"1994","journal-title":"Skin Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/toxsci\/kfg094","article-title":"Hepatocellular tumor induction in heterozygous p53-deficient CBA mice by a 26-week dietary administration of kojic acid","volume":"73","author":"Takizawa","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3892\/etm.2013.1249","article-title":"Evaluation of eye irritation by S-(\u2212)-10,11-dihydroxyfarnesic acid methyl ester secreted by Beauveria. bassiana CS1029","volume":"6","author":"Son","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00403-010-1089-5","article-title":"Ficus deltoidea (Mas cotek) extract exerted anti-melanogenic activity by preventing tyrosinase activity in vitro and by suppressing tyrosinase gene expression in B16F1 melanoma cells","volume":"303","author":"Oh","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_18","unstructured":"Image J Software 1.48 version. Available online:http:\/\/imagej.nih.gov\/ij\/download.html."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1590\/S0365-05962013000100009","article-title":"Mechanisms regulating melanogenesis","volume":"88","author":"Videira","year":"2013","journal-title":"Bras. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1038\/jid.2010.48","article-title":"Protection against UVR involves MC1R-mediated non-pigmentary and pigmentary mechanisms in vivo","volume":"130","author":"Robinson","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/pcmr.12059","article-title":"MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4","volume":"26","author":"Gunn","year":"2013","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s12272-013-0130-6","article-title":"The regulation of epidermal melanogenesis via cAMP and\/or PKC signaling pathways: Insights for the development","volume":"36","author":"Lee","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.0022-202X.2003.22134.x","article-title":"Topical application of a protein kinase C inhibitor reduces skin and hair pigmentation","volume":"122","author":"Park","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/exd.12248","article-title":"A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression","volume":"22","author":"Lee","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3892\/ijmm.2012.1028","article-title":"Wnt3a inhibits proliferation but promotes melanogenesis of Melan-a cells","volume":"30","author":"Guo","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1248\/cpb.54.281","article-title":"Regulation of melanin synthesis by selenium-containing carbohydrates","volume":"54","author":"Ahn","year":"2006","journal-title":"Chem. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1755-148X.2009.00588.x","article-title":"Evidence that stress to the epidermal barrier influenced the development of pigmentation in humans","volume":"22","author":"Elias","year":"2009","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1248\/bpb.31.33","article-title":"Down-regulation of tyrosinase expression by acetylsalicylic acid in murine B16 melanoma","volume":"31","author":"Sato","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.7164\/antibiotics.44.25","article-title":"Melanostatin, a new melanin synthesis inhibitor. Production, isolation, chemical properties, structure and biological activity","volume":"44","author":"Ishihara","year":"1991","journal-title":"J. Antibiot."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.3390\/ijms14011655","article-title":"Depigmentation effect of kadsuralignan F on Melan-a murine melanocytes and human skin equivalents","volume":"14","author":"Goh","year":"2013","journal-title":"Int. J. Mol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/7\/12750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:13:46Z","timestamp":1760217226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/7\/12750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,18]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2014,7]]}},"alternative-id":["ijms150712750"],"URL":"https:\/\/doi.org\/10.3390\/ijms150712750","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,18]]}}}