{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:46:23Z","timestamp":1770705983466,"version":"3.49.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2014,6]]},"DOI":"10.1016\/j.fct.2014.03.001","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T00:30:32Z","timestamp":1394757032000},"page":"38-43","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":41,"special_numbering":"C","title":["Betulinic acid isolated from Vitis amurensis root inhibits 3-isobutyl-1-methylxanthine induced melanogenesis via the regulation of MEK\/ERK and PI3K\/Akt pathways in B16F10 cells"],"prefix":"10.1016","volume":"68","author":[{"given":"Kyong-Suk","family":"Jin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You Na","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sook Kyung","family":"Hyun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Ju","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Woo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2014.03.001_b0005","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mrfmmm.2004.11.016","article-title":"Melanogenesis: a photoprotective response to DNA damage?","volume":"571","author":"Agar","year":"2005","journal-title":"Mutat. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0010","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0026-895X(25)15265-6","article-title":"Effects of xanthine derivatives on lipolysis and on adenosine 3\u2032,5\u2032-monophosphate phosphodiesterase activity","volume":"6","author":"Beavo","year":"1970","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.fct.2014.03.001_b0015","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1074\/jbc.M109.070573","article-title":"P38 regulates pigmentation via proteasomal degradation of tyrosinase","volume":"285","author":"Bellei","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2014.03.001_b0020","doi-asserted-by":"crossref","first-page":"R64","DOI":"10.1016\/j.cub.2004.12.058","article-title":"Beta-Catenin: a pivot between cell adhesion and Wnt signalling","volume":"15","author":"Bienz","year":"2005","journal-title":"Curr. Biol."},{"key":"10.1016\/j.fct.2014.03.001_b0025","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1034\/j.1600-0749.2003.00029.x","article-title":"Chemical and instrumental approaches to treat hyperpigmentation","volume":"16","author":"Briganti","year":"2003","journal-title":"Pigment Cell Res."},{"key":"10.1016\/j.fct.2014.03.001_b0030","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1142\/S0192415X08005758","article-title":"Inhibition of MITF and tyrosinase by paeonol-stimulated JNK\/SAPK to reduction of phosphorylated CREB","volume":"36","author":"Bu","year":"2008","journal-title":"Am. J. Chin. Med."},{"key":"10.1016\/j.fct.2014.03.001_b0035","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.bbagen.2012.03.018","article-title":"Evaluation of in vitro and in vivo anti-melanogenic activity of a newly synthesized strong tyrosinase inhibitor (E)-3-(2,4 dihydroxybenzylidene)pyrrolidine-2,5-dione (3-DBP)","volume":"1820","author":"Chung","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.fct.2014.03.001_b0040","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1096\/fj.06-6649rev","article-title":"Human skin pigmentation: melanocytes modulate skin color in response to stress","volume":"21","author":"Costin","year":"2007","journal-title":"FASEB J."},{"key":"10.1016\/j.fct.2014.03.001_b0045","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1529-8019.2007.00144.x","article-title":"Skin lightening preparations and the hydroquinone controversy","volume":"20","author":"Draelos","year":"2007","journal-title":"Dermatol. Ther."},{"key":"10.1016\/j.fct.2014.03.001_b0050","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/mnfr.200700491","article-title":"Betulinic acid: a natural product with anticancer activity","volume":"53","author":"Fulda","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.fct.2014.03.001_b0055","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1034\/j.1600-0749.2003.00057.x","article-title":"Microphthalmia-associated transcription factor (MITF) is required but is not sufficient to induce the expression of melanogenic genes","volume":"16","author":"Gaggioli","year":"2003","journal-title":"Pigment Cell Res."},{"key":"10.1016\/j.fct.2014.03.001_b0060","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jep.2009.06.019","article-title":"Antioxidant and lipoxygenase inhibitory activity of oligostilbenes from the leaf and stem of Vitis amurensis","volume":"125","author":"Ha do","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.fct.2014.03.001_b0065","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/10286029908039886","article-title":"Oligostilbenes from the roots of Vitis amurensis","volume":"2","author":"Huang","year":"1999","journal-title":"J. Asian Nat. Prod. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0070","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0031-9422(01)00224-2","article-title":"Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and the conformations of the seven-membered ring in some oligostilbenes","volume":"58","author":"Huang","year":"2001","journal-title":"Phytochemistry"},{"key":"10.1016\/j.fct.2014.03.001_b0075","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.phymed.2011.06.028","article-title":"Citrus flavanone naringenin enhances melanogenesis through the activation of Wnt\/beta-catenin signalling in mouse melanoma cells","volume":"18","author":"Huang","year":"2011","journal-title":"Phytomedicine"},{"key":"10.1016\/j.fct.2014.03.001_b0080","first-page":"287","article-title":"Partially purified Asiasari radix inhibits melanogenesis through extracellular signal-regulated kinase signaling in B16F10 cells","volume":"25","author":"Jang","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.fct.2014.03.001_b0085","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1007\/s12272-010-1015-6","article-title":"Leaf and stem of Vitis amurensis and its active components protect against amyloid beta protein (25\u201335)-induced neurotoxicity","volume":"33","author":"Jeong","year":"2010","journal-title":"Arch. Pharm. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0090","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1002\/ptr.3672","article-title":"Betulinic acid has an inhibitory effect on pancreatic lipase and induces adipocyte lipolysis","volume":"26","author":"Kim","year":"2012","journal-title":"Phytother. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0095","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1016\/j.lfs.2003.10.004","article-title":"Heyneanol A induces apoptosis via cytochrome c release and caspase activation in human leukemic U937 cells","volume":"74","author":"Lee","year":"2004","journal-title":"Life Sci."},{"key":"10.1016\/j.fct.2014.03.001_b0100","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.molmed.2006.07.008","article-title":"MITF: master regulator of melanocyte development and melanoma oncogene","volume":"12","author":"Levy","year":"2006","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.fct.2014.03.001_b0105","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0022-3565(25)12357-4","article-title":"Arbutin: mechanism of its depigmenting action in human melanocyte culture","volume":"276","author":"Maeda","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.fct.2014.03.001_b0110","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1056\/NEJMra052166","article-title":"Melanoma","volume":"355","author":"Miller","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.fct.2014.03.001_b0115","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4103\/0019-5154.108070","article-title":"A comparative study of the efficacy of 4% hydroquinone vs 0.75% kojic acid cream in the treatment of facial melisma","volume":"58","author":"Monteiro","year":"2013","journal-title":"Indian J. Dermatol."},{"key":"10.1016\/j.fct.2014.03.001_b0120","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/14786410601130794","article-title":"A new source of whitening agent from a Thai Mulberry plant and its betulinic acid quantitation","volume":"22","author":"Nattapong","year":"2008","journal-title":"Nat. Prod. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0125","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.mimet.2008.03.002","article-title":"WST-1-based cell cytotoxicity assay as a substitute for MTT-based assay for rapid detection of toxigenic Bacillus species using CHO cell line","volume":"73","author":"Ngamwongsatit","year":"2008","journal-title":"J. Microbiol. Meth."},{"key":"10.1016\/j.fct.2014.03.001_b0130","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/j.1755-148X.2009.00627.x","article-title":"Hear the Wnt Ror: how melanoma cells adjust to changes in Wnt","volume":"22","author":"O\u2019Connell","year":"2009","journal-title":"Pigment Cell Melanoma Res."},{"key":"10.1016\/j.fct.2014.03.001_b0135","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/j.1473-2165.2006.00253.x","article-title":"Hydroquinone and its analogues in dermatology \u2013 a risk-benefit viewpoint","volume":"5","author":"O\u2019Donoghue","year":"2006","journal-title":"J. Cosmet. Dermatol."},{"key":"10.1016\/j.fct.2014.03.001_b0140","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1042\/BJ20051388","article-title":"MITF mediates cAMP-induced protein kinase C-beta expression in human melanocytes","volume":"395","author":"Park","year":"2006","journal-title":"Biochem. J."},{"key":"10.1016\/j.fct.2014.03.001_b0145","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00403-011-1155-7","article-title":"Aromatic-turmerone inhibits alpha-MSH and IBMX-induced melanogenesis by inactivating CREB and MITF signaling pathways","volume":"303","author":"Park","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0150","first-page":"153","article-title":"Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions","volume":"22","author":"Pearson","year":"2001","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.fct.2014.03.001_b0155","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin pigmentation in mammalian skin and its hormonal regulation","volume":"84","author":"Slominski","year":"2004","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.fct.2014.03.001_b0160","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/(SICI)1099-1573(199903)13:2<115::AID-PTR404>3.0.CO;2-1","article-title":"In vitro and in vivo evaluation of betulinic acid as an antimalarial","volume":"13","author":"Steele","year":"1999","journal-title":"Phytother. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0165","doi-asserted-by":"crossref","first-page":"20443","DOI":"10.3390\/ijms141020443","article-title":"Inhibition of melanogenesis by gallic acid: possible involvement of the PI3K\/Akt, MEK\/ERK and Wnt\/beta-catenin signaling pathways in B16F10 cells","volume":"14","author":"Su","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.fct.2014.03.001_b0170","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1034\/j.1600-0749.2000.130404.x","article-title":"MITF: a stream flowing for pigment cells","volume":"13","author":"Tachibana","year":"2000","journal-title":"Pigment Cell Res."},{"key":"10.1016\/j.fct.2014.03.001_b0175","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1142\/S0192415X11009329","article-title":"Anti-inflammatory effects of Scoparia dulcis L. and betulinic acid","volume":"39","author":"Tsai","year":"2011","journal-title":"Am. J. Chin. Med."},{"key":"10.1016\/j.fct.2014.03.001_b0180","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/ptr.2216","article-title":"Tyrosinase inhibitory pentacyclic triterpenes and analgesic and spasmolytic activities of methanol extracts of Rhododendron collettianum","volume":"21","author":"Ullah","year":"2007","journal-title":"Phytother. Res."},{"key":"10.1016\/j.fct.2014.03.001_b0185","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1600-0625.2009.01053.x","article-title":"\u201cTranscription physiology\u201d of pigment formation in melanocytes: central role of MITF","volume":"19","author":"Vachtenheim","year":"2010","journal-title":"Exp. Dermatol."},{"key":"10.1016\/j.fct.2014.03.001_b0190","doi-asserted-by":"crossref","first-page":"27557","DOI":"10.1074\/jbc.R700026200","article-title":"The regulation of skin pigmentation","volume":"282","author":"Yamaguchi","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2014.03.001_b0195","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1034\/j.1600-0749.2001.140205.x","article-title":"Possible involvement of ERK 1\/2 in UVA-induced melanogenesis in cultured normal human epidermal melanocytes","volume":"14","author":"Yanase","year":"2001","journal-title":"Pigment Cell Res."},{"key":"10.1016\/j.fct.2014.03.001_b0200","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1271\/bbb.70088","article-title":"Involvement of extracellular signal-regulated kinase in nobiletin-induced melanogenesis in murine B16\/F10 melanoma cells","volume":"71","author":"Yoon","year":"2007","journal-title":"Biosci. Biotechnol. Biochem."}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691514001185?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691514001185?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T21:18:34Z","timestamp":1759526314000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691514001185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6]]},"references-count":40,"alternative-id":["S0278691514001185"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2014.03.001","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2014,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Betulinic acid isolated from Vitis amurensis root inhibits 3-isobutyl-1-methylxanthine induced melanogenesis via the regulation of MEK\/ERK and PI3K\/Akt pathways in B16F10 cells","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2014.03.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}