title: Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression.
abstract: 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 Piper longum was discovered to inhibit melanin production in melanoma B16 cells stimulated with alpha-melanocyte stimulating hormone (alpha-MSH), 3-isobutyl-1-methylxanthine or protoporphyrin IX, where the compound exhibited stronger depigmenting efficacy than kojic acid. However, piperlonguminine did not affect 1-oleoyl-2-acetyl-sn-glycerol-induced melanogenesis and did not affect protein kinase C-mediated melanin production. Surprisingly, piperlonguminine did not inhibit the catalytic activity of cell-free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase mRNA expression. This effect was attributed to the inhibitory action of piperlonguminine on alpha-MSH-induced signaling through cAMP to the cAMP responsive element binding protein that in turn regulates the expression of the microphthalmia-associated 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.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
authors.forename: Kyeong-Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Eom
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyung Rak
authors.initials: KR
authors.lastname: Min
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004148:Dioxolanes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism; D010881:Piperidones
chemical_list: D015056:1-Methyl-3-isobutylxanthine; D017362:Cyclic AMP Response Element-Binding Protein; D004075:Diglycerides; D004148:Dioxolanes; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase; D010726:Phosphodiesterase Inhibitors; D010936:Plant Extracts; D011524:Protoporphyrins; D012333:RNA, Messenger; D000521:alpha-MSH; C038237:1-oleoyl-2-acetylglycerol; C028025:protoporphyrin IX; C498077:piperlongumine; D010881:Piperidones