{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T17:07:32Z","timestamp":1781975252126,"version":"3.54.5"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"The National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Science, ICT & Future Planning, Republic of Korea","award":["NRF-2016R1A5A1011974"],"award-info":[{"award-number":["NRF-2016R1A5A1011974"]}]},{"name":"Ministry of Science, ICT & Future Planning, Republic of Korea","award":["2011-0030074"],"award-info":[{"award-number":["2011-0030074"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Kazinol U is a prenylated flavan isolated from an extract of <jats:styled-content style=\"fixed-case\"><jats:italic>Broussonetia kazinoki<\/jats:italic><\/jats:styled-content> Sieb (Moraceae). Kazinol U has shown cytoprotective effects against cytokine\u2010induced apoptotic cell death and induces AMP kinase (AMPK) activation through LKB1 activation. However, kazinol U has not been tested as a regulator of melanogenesis, although bark extract of <jats:styled-content style=\"fixed-case\"><jats:italic>B.\u00a0kazinoki<\/jats:italic><\/jats:styled-content> has been used as a cosmetic ingredient for skin conditioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We cultured mouse, human melanoma cells and normal human melanocytes to demonstrate anti\u2010melanogenic effects of kazinol U. A tyrosinase activity assay, Western blot, RT\u2010qPCR and a luciferase reporter gene assay were performed to determine the anti\u2010melanogenic mechanisms of kazinol U. We confirmed its effect on melanogenesis <jats:italic>in vivo<\/jats:italic> using zebrafish.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Kazinol U inhibited the expression and activity of tyrosinase, the rate\u2010limiting enzyme in melanogenesis, and reduced tyrosinase expression and activity in response to cAMP\u2010inducing agents. Kazinol U reduced the expression of other melanogenic enzymes, such as tyrosinase\u2010related protein (Tyrp) 1 and Tyrp2, and down\u2010regulated microphthalmia\u2010associated transcription factor (MITF), the master regulator of the tyrosinase gene family. Moreover, kazinol U induced phosphorylation of AMPK and MAPK proteins, which are MITF inhibitors. It also exhibited anti\u2010melanogenic effects in zebrafish, a recently developed <jats:italic>in vivo<\/jats:italic> model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our findings suggest that kazinol U reduces melanogenesis <jats:italic>via<\/jats:italic> its inhibitory effect on MITF and its downstream target genes, tyrosinase, Tyrp1 and Tyrp2. This work may provide a basis for the application of kazinol U for the treatment of hyperpigmentation skin disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14560","type":"journal-article","created":{"date-parts":[[2018,12,22]],"date-time":"2018-12-22T22:03:23Z","timestamp":1545516203000},"page":"737-750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Kazinol U inhibits melanogenesis through the inhibition of tyrosinase\u2010related proteins <i>via<\/i> AMP kinase activation"],"prefix":"10.1111","volume":"176","author":[{"given":"Jihyun","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Biological Science and Cellular Heterogeneity Research Center Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorim","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Cellular Heterogeneity Research Center Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hye","family":"Jeong","sequence":"additional","affiliation":[{"name":"Research Center for Cell Fate Control and College of Pharmacy Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Cellular Heterogeneity Research Center Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Cellular Heterogeneity Research Center Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong\u2010Sok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Cellular Heterogeneity Research Center Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Gu","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Center Korea Research Institute of Bioscience and Biotechnology  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Ha","family":"Ryu","sequence":"additional","affiliation":[{"name":"Research Center for Cell Fate Control and College of Pharmacy Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4024-6868","authenticated-orcid":false,"given":"Jong\u2010Seok","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Cellular Heterogeneity Research Center Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2010.00679.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700683"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.1026"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12765"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.11.022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.070573"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.185"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2009.00653.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2007.00365.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)00109-3"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00896.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1645908"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2494.2010.00616.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00050.2013"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802537200"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603114103"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606676200"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/10937400600882871"},{"key":"e_1_2_10_23_1","first-page":"119","article-title":"Suppression of \u03b1\u2010MSH and IBMX\u2010induced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K\/Akt and ERK\u2010dependent mechanisms","volume":"29","author":"Jin ML","year":"2012","journal-title":"Int J Mol Med"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2197"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2008.10.001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2008.00503.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.06.039"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3601"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00175"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.48.31801"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1994.tb00054.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-06-0077"},{"key":"e_1_2_10_34_1","first-page":"281","article-title":"Saponified sunflower and safflower oils inhibit melanogenesis in B16 melanoma cells","volume":"3","author":"Koo JH","year":"2010","journal-title":"Mol Med Rep"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.15272388"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.04.064"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.202"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13004"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2010.00775.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24379"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2000.130510.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2329"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.123729"},{"key":"e_1_2_10_44_1","first-page":"919","article-title":"Signaling pathways mediating melanogenesis","volume":"45","author":"Park HY","year":"1999","journal-title":"Cell Mol Biol (Noisy\u2010le\u2010Grand)"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141988"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1954"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2015.1039985"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3106"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00125.2012"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2009.00610.x"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00219.x"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2003"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.979"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2011.00898.x"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12618"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2091-15-23"},{"key":"e_1_2_10_57_1","volume-title":"The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio)","author":"Westerfield M","year":"2007"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206443"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160920240"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-962798"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.378"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.12.8058"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/np010283o"},{"key":"e_1_2_10_64_1","doi-asserted-by":"crossref","first-page":"56868","DOI":"10.18632\/oncotarget.18097","article-title":"Oleoylethanolamide inhibits \u03b1\u2010melanocyte stimulating hormone\u2010stimulated melanogenesis via ERK, Akt and CREB signaling pathways in B16 melanoma cells","volume":"8","author":"Zhou J","year":"2017","journal-title":"Oncotarget"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14560","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14560","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14560","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14560","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T19:54:53Z","timestamp":1694721293000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,28]]},"references-count":63,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/bph.14560"],"URL":"https:\/\/doi.org\/10.1111\/bph.14560","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,28]]},"assertion":[{"value":"2017-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}