{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:34:32Z","timestamp":1789655672174,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T00:00:00Z","timestamp":1131580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Research"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be improved by treatment with depigmenting agents. In the present study, piperlonguminine from <jats:italic>Piper longum<\/jats:italic> was discovered to inhibit melanin production in melanoma B16 cells stimulated with <jats:italic>\u03b1<\/jats:italic>\u2010melanocyte stimulating hormone (<jats:italic>\u03b1<\/jats:italic>\u2010MSH), 3\u2010isobutyl\u20101\u2010methylxanthine or protoporphyrin IX, where the compound exhibited stronger depigmenting efficacy than kojic acid. However, piperlonguminine did not affect 1\u2010oleoyl\u20102\u2010acetyl\u2010<jats:italic>sn<\/jats:italic>\u2010glycerol\u2010induced melanogenesis and did not affect protein kinase C\u2010mediated melanin production. Surprisingly, piperlonguminine did not inhibit the catalytic activity of cell\u2010free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase mRNA expression. This effect was attributed to the inhibitory action of piperlonguminine on <jats:italic>\u03b1<\/jats:italic>\u2010MSH\u2010induced signaling through cAMP to the cAMP responsive element binding protein that in turn regulates the expression of the microphthalmia\u2010associated transcription factor, a key activator of the tyrosinase promoter. This study demonstrates that piperlonguminine is an efficient depigmenting agent with a novel mechanism of action.<\/jats:p>","DOI":"10.1111\/j.1600-0749.2005.00281.x","type":"journal-article","created":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T17:04:43Z","timestamp":1131642283000},"page":"90-98","source":"Crossref","is-referenced-by-count":91,"title":["Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression"],"prefix":"10.1111","volume":"19","author":[{"given":"Kyeong\u2010Soo","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ah","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Yong","family":"Eom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Rak","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngsoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0781.2003.00034.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004030050320"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.134.3.747"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.2.694"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.1998.tb00324.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"15496","DOI":"10.1016\/S0021-9258(19)49562-8","article-title":"Inhibition by glucagon of the cGMP\u2010inhibited low\u2010Km cAMP phosphodiesterase in heart is mediated by a pertussis toxin\u2010sensitive G\u2010protein","volume":"267","author":"Brechler V.","year":"1992","journal-title":"J. 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