Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Melanogenesis inhibition activity of floralginsenoside A from Panax ginseng berry

  • Lee, Dae Young (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Lee, Jongsung (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Jeong, Yong Tae (Freshwater Bioresources Utilization Division, Nakdonggang National Institute of Biological Resources) ;
  • Byun, Geon Hee (College of Pharmacy, Kyungpook National University) ;
  • Kim, Jin Hee (College of Herbal Bio-industry, Daegu Haany University)
  • Received : 2016.05.09
  • Accepted : 2017.03.17
  • Published : 2017.10.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Panax ginseng is a traditional herb used for medicinal purposes in eastern Asia. P. ginseng contains various ginsenosides with pharmacological effects. In this study, floralginsenoside A (FGA), ginsenoside Rd (GRD), and ginsenoside Re (GRE) were purified from P. ginseng berry. Methods: Chemical structures of FGA, GRD, and GRE were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy, ID-nuclear magnetic resonance, and infrared spectroscopy. Inhibitory activities of these compounds on melanogenesis were studied by measuring the expression of protein and melanin content in the melan-a cell line. This inhibitory activity was confirmed by observing pigmentation and tyrosinase activities of zebrafish. Results: GRD, GRE, and FGA were not cytotoxic at concentrations less than $20{\mu}M$, $80{\mu}M$, and $160{\mu}M$ in melan-a cells, respectively. GRD, GRE, and FGA inhibited melanin biosynthesis in melan-a cells by 15.2%, 22.9%, and 23.9% at $20{\mu}M$, $80{\mu}M$, and $160{\mu}M$, respectively. FGA was observed to display the most potent inhibitory effect. In addition, FGA decreased microphthalmia-associated transcription factor protein expression in a dose-dependent manner. Moreover, FGA induced extracellular signal-regulated kinase phosphorylation level in melan-a cells. In addition, melanin pigment content and tyrosinase activity in zebrafish treated with FGA at $160{\mu}M$ were reduced. Conclusion: FGA showed the most potent inhibition of melanogenesis in both in vitro and in vivo studies. This study suggests that FGA purified from P. ginseng may be an effective melanogenesis inhibitor.

Keywords

References

  1. Kadekaro AL, Kavanagh R, Kanto H, Terzieva S, Hauser J, Kobayashi N, Schwemberger S, Cornelius J, Babcock G, Shertzer HG, et al. Alpha-melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes. Cancer Res 2005;65:4292-9. https://doi.org/10.1158/0008-5472.CAN-04-4535
  2. Chiang HM, Chien YC, Wu CH, Kuo YH, Wu WC, Pan YY, Su YH, Wen KC. Hydroalcoholic extract of Rhodiola rosea L. (Crassulaceae) and its hydrolysate inhibit melanogenesis in B16F0 cells by regulating the CREB/MITF/tyrosinase pathway. Food Chem Toxicol 2014;65:129-39. https://doi.org/10.1016/j.fct.2013.12.032
  3. Hearing Jr VJ. Mammalian monophenol monooxygenase (tyrosinase): purification, properties, and reactions catalyzed. Methods Enzymol 1987;142:154-65.
  4. Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003;16:101-10. https://doi.org/10.1034/j.1600-0749.2003.00029.x
  5. Fujimoto N, Watanabe H, Nakatani T, Roy G, Ito A. Induction of thyroid tumours in (C57BL/6N X C3H/N)F1 mice by oral administration of kojic acid. Food Chem Toxicol 1998;36:697-703. https://doi.org/10.1016/S0278-6915(98)00030-1
  6. Kim S, Jung SH, Cho CW. Physicochemical studies of a newly synthesized molecule, 6-methyl-3-phenethyl-3,4-dihydro-1h-quinazoline-2-thione (jsh18) for topical formulations. Arch Pharm Res 2008;31:1363-8. https://doi.org/10.1007/s12272-001-2118-x
  7. Choi S, Lee JH, Kim YI, Kang MJ, Rhim H, Lee SM, Nah SY. Effects of ginsenoside on g protein-coupled inwardly rectifying k+ channel activity expressed in xenopus oocytes. Eur J Pharmacol 2003;468:83-92. https://doi.org/10.1016/S0014-2999(03)01666-2
  8. Zhang C, Liu L, Yu Y, Chen B, Tang C, Li X. Antitumor effects of ginsenoside rg3 on human hepatocellular carcinoma cells. Mol Med Rep 2012;5:1295-8.
  9. Park D, Bae DK, Jeon JH, Lee J, Oh N, Yang G, Yang YH, Kim TK, Song J, Lee SH, et al. Immunopotentiation and antitumor effects of a ginsenoside Rg(3)-fortified red ginseng preparation in mice bearing H460 lung cancer cells. Environ Toxicol Pharmacol 2011;31:397-405. https://doi.org/10.1016/j.etap.2011.01.008
  10. Shin YM, Jung HJ, Choi WY, Lim CJ. Antioxidative, anti-inflammatory, and matrix metalloproteinase inhibitory activities of 20(s)-ginsenoside rg3 in cultured mammalian cell lines. Mol Bio Rep 2013;40:269-79. https://doi.org/10.1007/s11033-012-2058-1
  11. Kong YH, Jo YO, Cho CW, Son D, Park S, Rho J, Choi SY. Inhibitory effects of cinnamic acid on melanin biosynthesis in skin. Biol Pharm Bull 2008;31:946-8. https://doi.org/10.1248/bpb.31.946
  12. Im SJ, Kim KN, Yun YG, Lee JC, Mun YJ, Kim JH, Woo WH. Effect of radix ginseng and radix trichosanthis on the melanogenesis. Biol Pharm Bull 2003;26:849-53. https://doi.org/10.1248/bpb.26.849
  13. Lee Y, Kim KT, Kim SS, Hur J, Ha SK, Cho CW, Choi SY. Inhibitory effects of ginseng seed on melanin biosynthesis. Pharmacogn Mag 2014;10:S272-5. https://doi.org/10.4103/0973-1296.133271
  14. Xie JT, Shao ZH, Vanden Hoek TL, Chang WT, Li J, Mehendale S, Wang CZ, Hsu CW, Becker LB, Yin JJ, et al. Antioxidant effects of ginsenoside re in cardiomyocytes. Eur J Pharmacol 2006;532:201-7. https://doi.org/10.1016/j.ejphar.2006.01.001
  15. Zhang YX, Wang L, Xiao EL, Li SJ, Chen JJ, Gao B, Min GN, Wang ZP, Wu YJ. Ginsenoside-Rd exhibits anti-inflammatory activities through elevation of antioxidant enzyme activities and inhibition of JNK and ERK activation in vivo. Int Immunopharmacol 2013;17:1094-100. https://doi.org/10.1016/j.intimp.2013.10.013
  16. Yang CY, Wang J, Zhao Y, Shen L, Jiang X, Xie ZG, Liang N, Zhang L, Chen ZH. Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic components. J Ethnopharmacol 2010;130:231-6. https://doi.org/10.1016/j.jep.2010.04.039
  17. Mita A, Shida R, Kasai N, Shoji J. Enhancement and suppression in production of IgM-antibody in mice treated with purified saponins. Biomedicine 1979;31:223-7.
  18. Yoshikawa M, Sugimoto S, Nakamura S, Matsuda H. Medicinal flowers. Xi. Structures of new dammarane-type triterpene diglycosides with hydroperoxide group from flower buds of Panax ginseng. Chem Pharm Bull 2007;55:571-6. https://doi.org/10.1248/cpb.55.571
  19. Teng R, Li H, Chen J, Wang D, He Y, Yang C. Complete assignment of 1h and 13c NMR data for nine protopanaxatriol glycosides. Magn Reson Chem 2002;40:483-8. https://doi.org/10.1002/mrc.1033
  20. Sanada S, Kondo N, Shoji J, Tanaka O, Shibata S. Studies on the saponins of ginseng. I. Structures of ginsenoside-Ro, $-Rb_1$, $-Rb_2$, -Rc and -Rd. Chem Pharm Bull 1974;22:421-8. https://doi.org/10.1248/cpb.22.421
  21. Karlsson J, von Hofsten J, Olsson PE. Generating transparent zebrafish: a refined method to improve detection of gene expression during embryonic development. Mar Biotechnol 2001;3:522-7. https://doi.org/10.1007/s1012601-0053-4
  22. Choi TY, Kim JH, Ko DH, Kim CH, Hwang JS, Ahn S, Kim SY, Kim CD, Lee JH, Yoon TJ. Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds. Pigment Cell Res 2007;20:120-7. https://doi.org/10.1111/j.1600-0749.2007.00365.x
  23. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1-8. https://doi.org/10.1016/S0006-2952(97)00193-7
  24. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  25. Lee DY, Cha BJ, Lee YS, Kim GS, Noh HJ, Kim SY, Kang HC, Kim JH, Baek NI. The potential of minor ginsenosides isolated from the leaves of Panax ginseng as inhibitors of melanogenesis. Int J Mol Sci 2015;16:1677-90. https://doi.org/10.3390/ijms16011677
  26. Lee DY, Jeong SC, Jeong YT, Lee MK, Seo KH, Lee JW, Kim GS, Lee SE, Baek NI, Kim JH. Antimelanogenic effects of picrionoside a isolated from the leaves of Korean ginseng. Biol Pharm Bull 2015;38:1663-7. https://doi.org/10.1248/bpb.b15-00410
  27. Kim YJ, Uyama H. Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 2005;62:1707-23. https://doi.org/10.1007/s00018-005-5054-y
  28. Costin GE, Hearing VJ. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 2007;21:976-94. https://doi.org/10.1096/fj.06-6649rev
  29. Bentley NJ, Eisen T, Goding CR. Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator. Mol Cell Biol 1994;14:7996-8006. https://doi.org/10.1128/MCB.14.12.7996
  30. Shibahara S, Yasumoto KI, Amae S, Udono T, Watanabe KI, Saito H, Takeda K. Regulation of pigment cell-specific gene expression by MITF. Pigment Cell Melanoma Res 2000;13:98-102. https://doi.org/10.1034/j.1600-0749.13.s8.18.x
  31. Singh SK, Sarkar C, Mallick S, Saha B, Bera R, Bhadra R. Human placental lipid induces melanogenesis through p38 MAPK in B16F10 mouse melanoma. Pigment Cell Res 2005;18:113-21. https://doi.org/10.1111/j.1600-0749.2005.00219.x
  32. Solano F, Briganti S, Picardo M, Ghanem G. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res 2006;19:550-71. https://doi.org/10.1111/j.1600-0749.2006.00334.x
  33. Lee J, Jung K, Kim YS, Park D. Diosgenin inhibits melanogenesis through the activation of phosphatidylinositol-3-kinase pathway (pi3k) signaling. Life Sci 2007;81:249-54. https://doi.org/10.1016/j.lfs.2007.05.009
  34. Strahle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S, Schumacher A, Selderslaghs I, Weiss C, Witters H, et al. Zebrafish embryos as an alternative to animal experiments-a commentary on the definition of the onset of protected life stages in animal welfare regulations. Reprod Toxicol 2012;33:128-32. https://doi.org/10.1016/j.reprotox.2011.06.121
  35. Elsalini OA, Rohr KB. Phenylthiourea disrupts thyroid function in developing zebrafish. Dev Genes Evol 2003;212:593-8.
  36. Wang L, Lu AP, Yu ZL, Wong RN, Bian ZX, Kwok HH, Yue PY, Zhou LM, Chen H, Xu M, et al. The melanogenesis-inhibitory effect and the percutaneous formulation of ginsenoside Rb1. AAPS Pharm Sci Technol 2014;15:1252-62. https://doi.org/10.1208/s12249-014-0138-3
  37. Tung NH, Song GY, Nhiem NX, Ding Y, Tai BH, Jin LG, Lim CM, Hyun JW, Park CJ, Kang HK, et al. Dammarane-type saponins from the flower buds of Panax ginseng and their intracellular radical scavenging capacity. J Agric Food Chem 2010;58:868-74. https://doi.org/10.1021/jf903334g
  38. Tung NH, Quang TH, Son JH, Koo JE, Hong HJ, Koh YS, Song GY, Kim YH. Inhibitory effect of ginsenosides from steamed ginseng-leaves and flowers on the LPS-stimulated IL-12 production in bone marrow-derived dendritic cells. Arch Pharm Res 2011;34:681-5. https://doi.org/10.1007/s12272-011-0419-2

Cited by

  1. A Zebrafish Embryo as an Animal Model for the Treatment of Hyperpigmentation in Cosmetic Dermatology Medicine vol.54, pp.3, 2018, https://doi.org/10.3390/medicina54030035
  2. Oxidative Stress-Protective and Anti-Melanogenic Effects of Loliolide and Ethanol Extract from Fresh Water Green Algae, Prasiola japonica vol.19, pp.9, 2017, https://doi.org/10.3390/ijms19092825
  3. Pulsed Electromagnetic Fields Increase Pigmentation through the p-ERK/p-p38 Pathway in Zebrafish ( Danio rerio ) vol.19, pp.10, 2017, https://doi.org/10.3390/ijms19103211
  4. Rice Bran Ash Mineral Extract Increases Pigmentation through the p-ERK Pathway in Zebrafish ( Danio rerio ) vol.20, pp.9, 2017, https://doi.org/10.3390/ijms20092172
  5. Traditional Asian Herbs in Skin Whitening: The Current Development and Limitations vol.11, pp.None, 2020, https://doi.org/10.3389/fphar.2020.00982
  6. Antimelanogenic Activity of Ocotillol‐Type Saponins from Panax vietnamensis vol.17, pp.5, 2017, https://doi.org/10.1002/cbdv.202000037
  7. Advances in Saponin Diversity of Panax ginseng vol.25, pp.15, 2017, https://doi.org/10.3390/molecules25153452
  8. Anti-Pigmentary Natural Compounds and Their Mode of Action vol.22, pp.12, 2017, https://doi.org/10.3390/ijms22126206
  9. Antimelanogenesis Effects of Leaf Extract and Phytochemicals from Ceylon Olive (Elaeocarpus serratus) in Zebrafish Model vol.13, pp.7, 2017, https://doi.org/10.3390/pharmaceutics13071059