title: Effect of saucerneol D on melanin production in cAMP-elevated melanocytes.
abstract: Intracellular cAMP stimulates microphthalmia-associated transcription factor (MITF) induction in melanocytes through cAMP-responsive element binding protein (CREB), which plays a pivotal role in the gene expression of tyrosinase for melanin biosynthesis. In the present study, saucerneol D as a lignan constituent of Saururus chinensis (Saururaceae family) efficiently inhibited melanin production with IC(50) values of 188-297 nM in B16 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or other cAMP elevators. Moreover, saucerneol D down-regulated α-MSH-induced gene expression of tyrosinase at the transcription level in B16 cells, but it did not directly inhibit the catalytic activity of cell-free tyrosinase. As to the molecular basis of hypopigmenting action, saucerneol D inhibited α-MSH-induced phosphorylation of CREB in the cells, and sequentially suppressed MITF induction. Taken together, this study provides saucerneol D down-regulated the gene expression of tyrosinase, resulting in the inhibition of cAMP-induced melanin biosynthesis, and suggests pharmacological potential of the lignan structure in skin hyperpigmentation.
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
authors: Ji Young
authors: JY
authors: Yun
authors: Eunmiri
authors: E
authors: Roh
authors: Jong-Keun
authors: JK
authors: Son
authors: Seung Ho
authors: SH
authors: Lee
authors: Chang-Seob
authors: CS
authors: Seo
authors: Bang Yeon
authors: BY
authors: Hwang
authors: Sang-Bae
authors: SB
authors: Han
authors: Youngsoo
authors: Y
authors: Kim
mesh_terms: D002470:Cell Survival; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D032134:Saururaceae; D000521:alpha-MSH / Q000378:metabolism / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D006728:Hormones; D017705:Lignans; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C561428:saucerneol D; D000521:alpha-MSH; D000242:Cyclic AMP; D008156:Luciferases; D014442:Monophenol Monooxygenase