期刊论文详细信息
BMC Complementary and Alternative Medicine
Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells
Jin Yeul Ma1  Won-Kyung Cho1  Chun Liang1  Young Pil Jung1  Minju Im1  Nam-Hui Yim1  Aeyung Kim1 
[1] Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine (KIOM), 483 Expo-ro, Yuseong-gu, Daejeon 305-811, Republic of Korea
关键词: B16F10 cells;    Tyrosinase;    MITF;    PKA;    p38 MAPK;    Melanogenesis;    Ssanghwa-tang;   
Others  :  1221018
DOI  :  10.1186/1472-6882-13-214
 received in 2013-03-06, accepted in 2013-08-27,  发布年份 2013
PDF
【 摘 要 】

Background

Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.

Method

Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.

Results

SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.

Conclusion

SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.

【 授权许可】

   
2013 Kim et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150725134143129.pdf 1523KB PDF download
Figure 4. 72KB Image download
Figure 3. 108KB Image download
Figure 2. 102KB Image download
Figure 7. 136KB Image download
【 图 表 】

Figure 7.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Schallreuter KU, Kothari S, Chavan B, Spencer JD: Regulation of melanogenesis–controversies and new concepts. Exp Dermatol 2008, 17(5):395-404.
  • [2]Naish-Byfield S, Riley PA: Tyrosinase kinetics: failure of acceleration in oxidation of ring-blocked monohydric phenol substrate. Pigment Cell Res 1998, 11(2):94-97.
  • [3]Friedmann PS, Gilchrest BA: Ultraviolet radiation directly induces pigment production by cultured human melanocytes. J Cell Physiol 1987, 133(1):88-94.
  • [4]Busca R, Ballotti R: Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res 2000, 13(2):60-69.
  • [5]Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R: Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol 1998, 142(3):827-835.
  • [6]Costin GE, Hearing VJ: Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 2007, 21(4):976-994.
  • [7]Kim YJ, Kang KS, Yokozawa T: The anti-melanogenic effect of pycnogenol by its anti-oxidative actions. Food Chem Toxicol 2008, 46(7):2466-2471.
  • [8]Chang TS: An updated review of tyrosinase inhibitors. Int J Mol Sci 2009, 10(6):2440-2475.
  • [9]Nakagawa M, Kawai K: Contact allergy to kojic acid in skin care products. Contact Dermatitis 1995, 32(1):9-13.
  • [10]Shim KS, Lee JH, Ma CJ, Lee YH, Choi SU, Lee JH, Ma JY: Inhibitory effect of Ssangwha-tang on bone loss in ovariectomized rats. Animal Cell Syst 2010, 14:283-289.
  • [11]Han YH, Shim CK: Effect of a blended Korean herbal remedy, Ssang Wha Tang, on the liver cytoplasmic protein binding of sulfobromophthalein in rats. Phytother Res 1989, 3:109-111.
  • [12]Lv N, Koo JH, Yoon HY, Yu J, Kim KA, Choi IW, Kwon KB, Kwon KS, Kim HU, Park JW, et al.: Effect of Angelica gigas extract on melanogenesis in B16 melanoma cells. Int J Mol Med 2007, 20(5):763-767.
  • [13]Berry MN, Friend DS: High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol 1969, 43(3):506-520.
  • [14]Kim A, Yang Y, Lee MS, Yoo YD, Lee HG, Lim JS: NDRG2 gene expression in B16F10 melanoma cells restrains melanogenesis via inhibition of Mitf expression. Pigment Cell Melanoma Res 2008, 21(6):653-664.
  • [15]Yang MC, Kim DS, Ma JY: Bioconversion composition of Ssangwha-tang fermented by Lactobacillus fermentum. Biotechnol Bioproc Eng 2012, 17:84-92.
  • [16]Kim DS, Jeong YM, Park IK, Hahn HG, Lee HK, Kwon SB, Jeong JH, Yang SJ, Sohn UD, Park KC: A new 2-imino-1,3-thiazoline derivative, KHG22394, inhibits melanin synthesis in mouse B16 melanoma cells. Biol Pharm Bull 2007, 30(1):180-183.
  • [17]Smalley K, Eisen T: The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative effects in B16 murine melanoma cells. FEBS Lett 2000, 476(3):198-202.
  • [18]Saha B, Singh SK, Sarkar C, Bera R, Ratha J, Tobin DJ, Bhadra R: Activation of the Mitf promoter by lipid-stimulated activation of p38-stress signalling to CREB. Pigment Cell Res 2006, 19(6):595-605.
  • [19]Jang JY, Kim HN, Kim YR, Choi YH, Kim BW, Shin HK, Choi BT: Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through inhibition of the p38 mitogen-activated protein kinase signaling pathway in B16F10 cells. J Ethnopharmacol 2012, 141(1):338-344.
  • [20]Ye Y, Chu JH, Wang H, Xu H, Chou GX, Leung AK, Fong WF, Yu ZL: Involvement of p38 MAPK signaling pathway in the anti-melanogenic effect of San-bai-tang, a Chinese herbal formula, in B16 cells. J Ethnopharmacol 2010, 132(2):533-535.
  • [21]Corson TW, Crews CM: Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell 2007, 130(5):769-774.
  • [22]Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ: The challenge of finding a cure for HIV infection. Science 2009, 323(5919):1304-1307.
  • [23]Kiyohara H, Matsumoto T, Yamada H: Combination effects of herbs in a multi-herbal formula: expression of Juzen-taiho-to's immuno-modulatory activity on the intestinal immune system. Evid base Compl Alternative Med 2004, 1(1):83-91.
  • [24]Matsuda H, Murata K, Itoh K, Masuda M, Naruto S: Melanin Hyperpigmentation Inhibitors from Natural Resources. Advances in Malignant Melanoma-Clinical and Research Perspectives 2011, 171-184.
  • [25]Lee KT, Kim BJ, Kim JH, Heo MY, Kim HP: Biological screening of 100 plant extracts for cosmetic use (I): inhibitory activities of tyrosinase and DOPA auto-oxidation. Int J Cosmet Sci 1997, 19(6):291-298.
  • [26]Jeong JA, Kwon SH, Kim YJ, Shin CS, Lee CH: Investigation of antioxidative and tyrosinase inhibitory activities of the seed extracts. Kor J Plant Res 2007, 20(2):177-188.
  • [27]Jung YO, Park NB, Jung SJ, Kwak JS, Han JH: Effect of whitening, anti-aging on extract of Paeonia lactiflora flower. Kor J Ori Med Physiol Pathol 2010, 24(3):452-456.
  • [28]Kim DS, Park SH, Lee HK, Choo SJ, Lee JH, Song GY, Yoo ID, Kwon SB, Na JI, Park KC: Hypopigmentary action of dihydropyranocoumarin D2, a decursin derivative, as a MITF-degrading agent. J Nat Prod 2010, 73(5):797-800.
  • [29]Lee K, Lee JH, Boovanahalli SK, Choi Y, Choo SJ, Yoo ID, Kim DH, Yun MY, Lee GW, Song GY: Synthesis of (S)-(+)-decursin and its analogues as potent inhibitors of melanin formation in B16 murine melanoma cells. Eur J Med Chem 2010, 45(12):5567-5575.
  • [30]Okabe Y, Shimazu T, Tanimoto H: Higher bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans compared with glucoside-rich non-fermented soybeans in Japanese postmenopausal women. J Sci Food Agric 2011, 91(4):658-663.
  文献评价指标  
  下载次数:76次 浏览次数:28次