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http://dx.doi.org/10.5142/jgr.2013.37.389

Inhibitory effect of Korean Red Ginseng on melanocyte proliferation and its possible implication in GM-CSF mediated signaling  

Oh, Chang Taek (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Park, Jong Il (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Jung, Yi Ra (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Joo, Yeon Ah (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Shin, Dong Ha (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Cho, Hyoung Joo (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Ahn, Soo Mi (Skin Biotechnology Center, Kyung Hee University)
Lim, Young-Ho (KGC R&D Headquarters)
Park, Chae Kyu (KGC R&D Headquarters)
Hwang, Jae Sung (Department of Genetic Engineering, College of Life Science, Kyung Hee University)
Publication Information
Journal of Ginseng Research / v.37, no.4, 2013 , pp. 389-400 More about this Journal
Abstract
Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation ($30mJ/cm^2$), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte-conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation.
Keywords
Panax ginseng; Korean Red Ginseng; Ultraviolet radiation; Skin pigmentation; Granulocyte-macrophage colony-stimulating factor;
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1 Imokawa G, Kobayasi T, Miyagishi M. Intracellular signaling mechanisms leading to synergistic effects of endothelin-1 and stem cell factor on proliferation of cultured human melanocytes. Cross-talk via trans-activation of the tyrosine kinase c-kit receptor. J Biol Chem 2000; 275:33321-33328.   DOI   ScienceOn
2 Funasaka Y, Chakraborty AK, Hayashi Y, Komoto M, Ohashi A, Nagahama M, Inoue Y, Pawelek J, Ichihashi M. Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1alpha, interleukin-1beta, endothelin-1 and tumour necrosis factor-alpha. Br J Dermatol 1998;139:216-224.   DOI   ScienceOn
3 Hachiya A, Kobayashi A, Yoshida Y, Kitahara T, Takema Y, Imokawa G. Biphasic expression of two paracrine melanogenic cytokines, stem cell factor and endothelin-1, in ultraviolet B-induced human melanogenesis. Am J Pathol 2004;165:2099-2109.   DOI   ScienceOn
4 Hirobe T, Furuya R, Hara E, Horii I, Tsunenaga M, Ifuku O. Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls the proliferation and differentiation of mouse epidermal melanocytes from pigmented spots induced by ultraviolet radiation B. Pigment Cell Res 2004;17:230-240.   DOI   ScienceOn
5 Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal- regulated kinase activation. Cell 1995;80:179-185.   DOI   ScienceOn
6 Eimpunth S, Wanitphadeedecha R, Manuskiatti W. A focused review on acne-induced and aesthetic procedure- related postinflammatory hyperpigmentation in Asians. J Eur Acad Dermatol Venereol 2013;27 Suppl 1:7-18.
7 Bennett DC, Cooper PJ, Hart IR. A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth. Int J Cancer 1987;39:414-418.   DOI
8 Strickland JE, Greenhalgh DA, Koceva-Chyla A, Hennings H, Restrepo C, Balaschak M, Yuspa SH. Development of murine epidermal cell lines which contain an activated rasHa oncogene and form papillomas in skin grafts on athymic nude mouse hosts. Cancer Res 1988;48:165-169.
9 Cabanes J, Chazarra S, Garcia-Carmona F. Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase. J Pharm Pharmacol 1994;46:982-985.   DOI   ScienceOn
10 Marini A, Farwick M, Grether-Beck S, Brenden H, Felsner I, Jaenicke T, Weber M, Schild J, Maczkiewitz U, Kohler T et al. Modulation of skin pigmentation by the tetrapeptide PKEK: in vitro and in vivo evidence for skin whitening effects. Exp Dermatol 2012;21:140-146.   DOI   ScienceOn
11 Brouxhon S, Konger RL, VanBuskirk J, Sheu TJ, Ryan J, Erdle B, Almudevar A, Breyer RM, Scott G, Pentland AP. Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness. J Invest Dermatol 2007;127:439-446.   DOI   ScienceOn
12 Gasson JC, Weisbart RH, Kaufman SE, Clark SC, Hewick RM, Wong GG, Golde DW. Purified human granulocyte- macrophage colony-stimulating factor: direct action on neutrophils. Science 1984;226:1339-1342.   DOI
13 Morstyn G, Burgess AW. Hemopoietic growth factors: a review. Cancer Res 1988;48:5624-5637.
14 Wong GG, Witek JS, Temple PA, Wilkens KM, Leary AC, Luxenberg DP, Jones SS, Brown EL, Kay RM, Orr EC et al. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science 1985;228:810-815.   DOI
15 Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P, Mantovani A. Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 1989;337:471-473.   DOI   ScienceOn
16 Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16 Suppl:S3-S5.   DOI
17 Mann A, Breuhahn K, Schirmacher P, Blessing M. Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing: stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization. J Invest Dermatol 2001;117:1382-1390.   DOI
18 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-1693.   DOI   ScienceOn
19 Tachikawa E, Kudo K, Harada K, Kashimoto T, Miyate Y, Kakizaki A, Takahashi E. Effects of ginseng saponins on responses induced by various receptor stimuli. Eur J Pharmacol 1999;369:23-32.   DOI   ScienceOn
20 Yin H, Park SA, Park SJ, Han SK. Korean red ginseng extract activates non-NMDA glutamate and GABAA receptors on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. J Ginseng Res 2011;35:219-225.   DOI   ScienceOn
21 Lee KG, Son SW. Efficacy of Korean red ginseng in the treatment of atopic dermatitis. J Ginseng Res 2011; 35:149-154.   과학기술학회마을   DOI   ScienceOn
22 Yang H, Lee SE, Jeong SI, Park CS, Jin YH, Park YS. Up-regulation of heme oxygenase-1 by Korean red ginseng water extract as a cytoprotective effect in human endothelial cells. J Ginseng Res 2011;35:352-359.   과학기술학회마을   DOI   ScienceOn
23 Surh YJ, Ferguson LR. Dietary and medicinal antimutagens and anticarcinogens: molecular mechanisms and chemopreventive potential--highlights of a symposium. Mutat Res 2003;523-524:1-8.   DOI   ScienceOn
24 Xiang YZ, Shang HC, Gao XM, Zhang BL. A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother Res 2008;22:851-858.   DOI   ScienceOn
25 Jin SH, Park JK, Nam KY, Park SN, Jung NP. Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. J Ethnopharmacol 1999;66:123-129.   DOI   ScienceOn
26 Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ. Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin 2000;21:1095-1100.
27 Kaneko H, Nakanishi K. Proof of the mysterious efficacy of ginseng: basic and clinical trials: clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J Pharmacol Sci 2004;95:158-162.   DOI   ScienceOn
28 Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 2008;18:46-56.   DOI   ScienceOn
29 Choi HK, Seong DH, Rha KH. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impot Res 1995;7:181-186.
30 De Andrade E, de Mesquita AA, Claro Jde A, de Andrade PM, Ortiz V, Paranhos M, Srougi M. Study of the efficacy of Korean red ginseng in the treatment of erectile dysfunction. Asian J Androl 2007;9:241-244.   DOI   ScienceOn
31 Jung HL, Kwak HE, Kim SS, Kim YC, Lee CD, Byurn HK, Kang HY. Effects of Panax ginseng supplementation on muscle damage and inflammation after uphill treadmill running in humans. Am J Chin Med 2011;39:441-450.   DOI   ScienceOn
32 Cho E, Cho SH. Effects of Korean red ginseng extract on the prevention of atopic dermatitis and its mechanism on early lesions in a murine model. J Ethnopharmacol 2013;145:294-302.   DOI   ScienceOn
33 Lee HS, Kim MR, Park Y, Park HJ, Chang UJ, Kim SY, Suh HJ. Fermenting red ginseng enhances its safety and efficacy as a novel skin care anti-aging ingredient: in vitro and animal study. J Med Food 2012;15:1015-1023.   DOI   ScienceOn
34 Han BH, Park MH, Han YN. Studies on the anti-oxidant components of Korean ginseng. In: Korea Ginseng Research Institute. Proceedings of 2nd International Ginseng Symposium; Seoul, Korea. Seoul: Korea Ginseng Research Institute, 1978. p.13-17.
35 Sugai T. Clinical effects of arbutin in patients with cholasma. Skin Res 1992;34:522.
36 Mishima Y, Imokawa G. Selective aberration and pigment loss in melanosomes of malignant melanoma cells in vitro by glycosylation inhibitors: premelanosomes as glycoprotein. J Invest Dermatol 1983;81:106-114.   DOI   ScienceOn
37 Imokawa G, Mishima Y. Loss of melanogenic properties in tyrosinases induced by glucosylation inhibitors within malignant melanoma cells. Cancer Res 1982;42:1994-2002.
38 Hearing VJ. Biochemical control of melanogenesis and melanosomal organization. J Investig Dermatol Symp Proc 1999;4:24-28.   DOI   ScienceOn
39 Imokawa G, Kawai M, Mishima Y, Motegi I. Differential analysis of experimental hypermelanosis induced by UVB, PUVA, and allergic contact dermatitis using a brownish guinea pig model. Arch Dermatol Res 1986; 278:352-362.   DOI   ScienceOn
40 Abdel-Malek Z, Swope V, Smalara D, Babcock G, Dawes S, Nordlund J. Analysis of the UV-induced melanogenesis and growth arrest of human melanocytes. Pigment Cell Res 1994;7:326-332.   DOI   ScienceOn
41 Rosdahl IK, Szabo G. Mitotic activity of epidermal melanocytes in UV-irradiated mouse skin. J Invest Dermatol 1978;70:143-148.   DOI   ScienceOn
42 Dissanayake NS, Greenoak GE, Mason RS. Effects of ultraviolet irradiation on human skin-derived epidermal cells in vitro. J Cell Physiol 1993;157:119-127.   DOI   ScienceOn
43 Gilchrest BA, Park HY, Eller MS, Yaar M. Mechanisms of ultraviolet light-induced pigmentation. Photochem Photobiol 1996;63:1-10.   DOI   ScienceOn
44 Yamaguchi Y, Hearing VJ. Melanocyte distribution and function in human skin: effects of UV radiation. In: Hearing VJ, Leong SP, eds. Melanocytes to malignant melanoma: the progression to malignancy. Totowa: Humana Press, 2006. p.101-115.
45 Matsumura Y, Ananthaswamy HN. Toxic effects of ultraviolet radiation on the skin. Toxicol Appl Pharmacol 2004;195:298-308.   DOI   ScienceOn
46 Gloster HM Jr, Brodland DG. The epidemiology of skin cancer. Dermatol Surg 1996;22:217-226.
47 Ullrich SE. Mechanisms underlying UV-induced immune suppression. Mutat Res 2005;571:185-205.   DOI   ScienceOn
48 Cox NH, Diffey BL, Farr PM. The relationship between chronological age and the erythemal response to ultraviolet B radiation. Br J Dermatol 1992;126:315-319.   DOI   ScienceOn
49 Gilchrest BA. A review of skin ageing and its medical therapy. Br J Dermatol 1996;135:867-875.   DOI   ScienceOn
50 Furuya R, Akiu S, Ideta R, Naganuma M, Fukuda M, Hirobe T. Changes in the proliferative activity of epidermal melanocytes in serum-free primary culture during the development of ultraviolet radiation B-induced pigmented spots in hairless mice. Pigment Cell Res 2002;15:348-356.   DOI   ScienceOn
51 Furuya R, Yoshida Y, Moro O, Tsunenaga M, Aoki H, Kishimoto J, Ifuku O, Hirobe T. Immunohistochemical survey of the distribution of epidermal melanoblasts and melanocytes during the development of UVB-induced pigmented spots. J Dermatol Sci 2009;55:99-107.   DOI   ScienceOn
52 Hirobe T. Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes. Pigment Cell Res 2005;18:2-12.   DOI   ScienceOn
53 Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res 2004;17:96-110.   DOI   ScienceOn
54 Naganumaa M, Yagi E, Fukuda M. Delayed induction of pigmented spots on UVB-irradiated hairless mice. J Dermatol Sci 2001;25:29-35.   DOI   ScienceOn
55 Kupper TS, Chua AO, Flood P, McGuire J, Gubler U. Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation. J Clin Invest 1987;80:430-436.   DOI
56 Enk CD, Sredni D, Blauvelt A, Katz SI. Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro. J Immunol 1995;154:4851-4856.
57 Kock A, Schwarz T, Kirnbauer R, Urbanski A, Perry P, Ansel JC, Luger TA. Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. J Exp Med 1990;172:1609-1614.   DOI   ScienceOn
58 Halaban R, Langdon R, Birchall N, Cuono C, Baird A, Scott G, Moellmann G, McGuire J. Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes. J Cell Biol 1988;107:1611-1619.   DOI   ScienceOn