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Int. J. Mol. Sci. 2017, 18(2), 471; doi:10.3390/ijms18020471

Gomisin N Inhibits Melanogenesis through Regulating the PI3K/Akt and MAPK/ERK Signaling Pathways in Melanocytes

1
College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea
2
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea
3
Department of Applied Chemistry and Institute of Natural Sciences, Kyung Hee University, Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyenggi-do 17104, Korea
4
Gachon Medical Research Institute, Gil Medical Center, Inchon 21565, Korea
5
Gachon Institute of Pharmaceutical Science, Gachon University; #191 Hambakmoe-ro, Yeonsu-gu, Incheon 21565, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Manickam Sugumaran
Received: 20 December 2016 / Revised: 9 February 2017 / Accepted: 13 February 2017 / Published: 22 February 2017
(This article belongs to the Special Issue Biochemistry and Mechanisms of Melanogenesis)
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Abstract

Gomisin N, one of the lignan compounds found in Schisandra chinensis has 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. View Full-Text
Keywords: Schisandra chinensis; Gomisin N; lignan; melanogenesis; skin whitening Schisandra chinensis; Gomisin N; lignan; melanogenesis; skin whitening
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MDPI and ACS Style

Chae, J.K.; Subedi, L.; Jeong, M.; Park, Y.U.; Kim, C.Y.; Kim, H.; Kim, S.Y. Gomisin N Inhibits Melanogenesis through Regulating the PI3K/Akt and MAPK/ERK Signaling Pathways in Melanocytes. Int. J. Mol. Sci. 2017, 18, 471.

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