title: Gomisin N Inhibits Melanogenesis through Regulating the PI3K/Akt and MAPK/ERK Signaling Pathways in Melanocytes.
abstract: Gomisin N, one of the lignan compounds found inSchisandra chinensishas been shown to possess anti-oxidative, anti-tumorigenic, and anti-inflammatory activities in various studies. Here we report, for the first time, the anti-melenogenic efficacy of Gomisin N in mammalian cells as well as in zebrafish embryos. Gomisin N significantly reduced the melanin content without cellular toxicity. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, Gomisin N downregulated the expression levels of key proteins that function in melanogenesis. Gomisin N downregulated melanocortin 1 receptor (MC1R), adenylyl cyclase 2, microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). In addition, Gomisin N-treated Melan-A cells exhibited increased p-Akt and p-ERK levels, which implies that the activation of the PI3K/Akt and MAPK/ERK pathways may function to inhibit melanogenesis. We also validated that Gomisin N reduced melanin production by repressing the expression of MITF, tyrosinase, TRP-1, and TRP-2 in mouse and human cells as well as in developing zebrafish embryos. Collectively, we conclude that Gomisin N inhibits melanin synthesis by repressing the expression of MITF and melanogenic enzymes, probably through modulating the PI3K/Akt and MAPK/ERK pathways.
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. jae1990@nate.com.
authors.forename: Jae Kyoung
authors.initials: JK
authors.lastname: Chae
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. subedilali@gmail.com.
authors.forename: Lalita
authors.initials: L
authors.lastname: Subedi
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. minsun.jeong@gmail.com.
authors.forename: Minsun
authors.initials: M
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. kong_park@naver.com.
authors.forename: Yong Un
authors.initials: YU
authors.lastname: Park
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea. chulykim@hanyang.ac.kr.
authors.forename: Chul Young
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Applied Chemistry and Institute of Natural Sciences, Kyung Hee University, Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyenggi-do 17104, Korea. hwkim@khu.ac.kr.
authors.forename: Hakwon
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. sunnykim@gachon.ac.kr.|Gachon Medical Research Institute, Gil Medical Center, Inchon 21565, Korea. sunnykim@gachon.ac.kr.|Gachon Institute of Pharmaceutical Science, Gachon University; #191 Hambakmoe-ro, Yeonsu-gu, Incheon 21565, Korea. sunnykim@gachon.ac.kr.
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D034242:Cyclooctanes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D008543:Melanins; D011083:Polycyclic Compounds; D044102:Receptor, Melanocortin, Type 1; C015499:schizandrin B; D014442:Monophenol Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Gomisin N; Schisandra chinensis; lignan; melanogenesis; skin whitening