Skip to main content
SpringerLink
Log in

Effects of resveratrol, oxyresveratrol, and their acetylated derivatives on cellular melanogenesis

Archives of Dermatological Research volume 306, pages 475–487 (2014)Cite this article

Abstract

Resveratrol and oxyresveratrol are naturally occurring phenolic compounds with various bioactivities, but their uses in cosmetics have been partly limited by their chemical instabilities. This study was performed to examine the anti-melanogenic effects of the acetylated derivatives from resveratrol and oxyresveratrol. Resveratrol and oxyresveratrol were chemically modified to triacetyl resveratrol and tetraacetyl oxyresveratrol, respectively. The acetylated compounds were less susceptible than the parent compounds to oxidative discoloration. The acetylated compounds inhibited the activities of tyrosinases less than parent compounds in vitro, but they were as effective at cellular melanogenesis inhibition, indicating bioconversion to parent compounds inside cells. Supporting this notion, the parent compounds were regenerated when the acetylated compounds were digested with cell lysates. Although resveratrol and triacetyl resveratrol inhibited tyrosinase activity less effectively than oxyresveratrol and tetraacetyl oxyresveratrol in vitro, they inhibited cellular melanogenesis more effectively. This discrepancy was explained by strong inhibition of tyrosinase expression by resveratrol and triacetyl resveratrol. Experiments using a reconstituted skin model indicated that resveratrol derivatives can affect melanin synthesis and cell viability to different extents. Collectively, this study suggests that acetylated derivatives of resveratrol have great potential as anti-melanogenic agents for cosmetic use in terms of efficacy, safety, and stability.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

  1. An SM, Kim HJ, Kim JE, Boo YC (2008) Flavonoids, taxifolin and luteolin attenuate cellular melanogenesis despite increasing tyrosinase protein levels. Phytother Res 22:1200–1207

    Article  CAS  PubMed  Google Scholar 

  2. An SM, Lee SI, Choi SW, Moon SW, Boo YC (2008) p-Coumaric acid, a constituent of Sasa quelpaertensis Nakai, inhibits cellular melanogenesis stimulated by alpha-melanocyte stimulating hormone. Br J Dermatol 159:292–299

    Article  CAS  PubMed  Google Scholar 

  3. An SM, Koh JS, Boo YC (2009) Inhibition of melanogenesis by tyrosinase siRNA in human melanocytes. BMB Rep 42:178–183

    Article  CAS  PubMed  Google Scholar 

  4. An SM, Koh JS, Boo YC (2010) p-Coumaric acid not only inhibits human tyrosinase activity in vitro but also melanogenesis in cells exposed to UVB. Phytother Res 24:1175–1180

    CAS  PubMed  Google Scholar 

  5. Busca R, Ballotti R (2000) Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res 13:60–69

    Article  CAS  PubMed  Google Scholar 

  6. Cabanes J, Chazarra S, Garcia-Carmona F (1994) Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase. J Pharm Pharmacol 46:982–985

    Article  CAS  PubMed  Google Scholar 

  7. Caddeo C, Teskac K, Sinico C, Kristl J (2008) Effect of resveratrol incorporated in liposomes on proliferation and UV-B protection of cells. Int J Pharm 363:183–191

    Article  CAS  PubMed  Google Scholar 

  8. Cardinali G, Ceccarelli S, Kovacs D, Aspite N, Lotti LV, Torrisi MR, Picardo M (2005) Keratinocyte growth factor promotes melanosome transfer to keratinocytes. J Invest Dermatol 125:1190–1199

    Article  CAS  PubMed  Google Scholar 

  9. Chang TS (2009) An updated review of tyrosinase inhibitors. Int J Mol Sci 10:2440–2475

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Costin GE, Hearing VJ (2007) Human skin pigmentation: melanocytes modulate skin color in response to stress. Faseb J 21:976–994

    Article  CAS  PubMed  Google Scholar 

  11. Ebanks JP, Wickett RR, Boissy RE (2009) Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration. Int J Mol Sci 10:4066–4087

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Epstein JH (1983) Photocarcinogenesis, skin cancer, and aging. J Am Acad Dermatol 9:487–502

    Article  CAS  PubMed  Google Scholar 

  13. Hsieh TC, Huang YC, Wu JM (2011) Control of prostate cell growth, DNA damage and repair and gene expression by resveratrol analogues, in vitro. Carcinogenesis 32:93–101

    Article  CAS  PubMed  Google Scholar 

  14. Kim HJ, An SM, Boo YC (2008) A dual mechanism of 4-hydroxy-5-methyl-3[2H]-furanone inhibiting cellular melanogenesis. J Cosmet Sci 59:117–125

    CAS  PubMed  Google Scholar 

  15. Kim M, An SM, Koh JS, Jang DI, Boo YC (2011) Use of non-melanocytic HEK293 cells stably expressing human tyrosinase for the screening of anti-melanogenic agents. J Cosmet Sci 62:515–523

    CAS  PubMed  Google Scholar 

  16. Kim M, Park J, Song K, Kim HG, Koh JS, Boo YC (2012) Screening of plant extracts for human tyrosinase inhibiting effects. Int J Cosmet Sci 34:202–208

    Article  CAS  PubMed  Google Scholar 

  17. Kim YJ, Uyama H (2005) Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 62:1707–1723

    Article  CAS  PubMed  Google Scholar 

  18. Kim YM, Yun J, Lee CK, Lee H, Min KR, Kim Y (2002) Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action. J Biol Chem 277:16340–16344

    Article  CAS  PubMed  Google Scholar 

  19. Kwon BS, Haq AK, Pomerantz SH, Halaban R (1987) Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci USA 84:7473–7477

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Lebonvallet N, Jeanmaire C, Danoux L, Sibille P, Pauly G, Misery L (2010) The evolution and use of skin explants: potential and limitations for dermatological research. Eur J Dermatol 20:671–684

    PubMed  Google Scholar 

  21. Lee KT, Lee KS, Jeong JH, Jo BK, Heo MY, Kim HP (2003) Inhibitory effects of Ramulus mori extracts on melanogenesis. J Cosmet Sci 54:133–142

    CAS  PubMed  Google Scholar 

  22. Lin CB, Babiarz L, Liebel F, Roydon Price E, Kizoulis M, Gendimenico GJ, Fisher DE, Seiberg M (2002) Modulation of microphthalmia-associated transcription factor gene expression alters skin pigmentation. J Invest Dermatol 119:1330–1340

    Google Scholar 

  23. Maeda K, Fukuda M (1996) Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 276:765–769

    CAS  PubMed  Google Scholar 

  24. Newton RA, Cook AL, Roberts DW, Leonard JH, Sturm RA (2007) Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes. J Invest Dermatol 127:2216–2227

    Article  CAS  PubMed  Google Scholar 

  25. Olivares C, Solano F (2009) New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins. Pigment Cell Melanoma Res 22:750–760

    Article  CAS  PubMed  Google Scholar 

  26. Park J, Boo YC (2013) Isolation of resveratrol from vitis viniferae caulis and its potent inhibition of human tyrosinase. Evid Based Complement Alternat Med 2013:645257

    PubMed Central  PubMed  Google Scholar 

  27. Park SH, Kim DS, Park SH, Shin JW, Youn SW, Park KC (2008) Inhibitory effect of p-coumaric acid by Rhodiola sachalinensis on melanin synthesis in B16F10 cells. Pharmazie 63:290–295

    CAS  PubMed  Google Scholar 

  28. Petrovski G, Gurusamy N, Das DK (2011) Resveratrol in cardiovascular health and disease. Ann N Y Acad Sci 1215:22–33

    Article  PubMed  Google Scholar 

  29. Satooka H, Kubo I (2012) Resveratrol as a kcat type inhibitor for tyrosinase: potentiated melanogenesis inhibitor. Bioorg Med Chem 20:1090–1099

    Article  CAS  PubMed  Google Scholar 

  30. Schiaffino MV (2010) Signaling pathways in melanosome biogenesis and pathology. Int J Biochem Cell Biol 42:1094–1104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Schwahn DJ, Xu W, Herrin AB, Bales ES, Medrano EE (2001) Tyrosine levels regulate the melanogenic response to alpha-melanocyte-stimulating hormone in human melanocytes: implications for pigmentation and proliferation. Pigment Cell Res 14:32–39

    Article  CAS  PubMed  Google Scholar 

  32. Seo YK, Kim SJ, Boo YC, Baek JH, Lee SH, Koh JS (2011) Effects of p-coumaric acid on erythema and pigmentation of human skin exposed to ultraviolet radiation. Clin Exp Dermatol 36:260–266

    Article  CAS  PubMed  Google Scholar 

  33. Silva F, Figueiras A, Gallardo E, Nerin C, Domingues FC (2014) Strategies to improve the solubility and stability of stilbene antioxidants: a comparative study between cyclodextrins and bile acids. Food Chem 145:115–125

    Article  CAS  PubMed  Google Scholar 

  34. Slominski A, Tobin DJ, Shibahara S, Wortsman J (2004) Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84:1155–1228

    Article  CAS  PubMed  Google Scholar 

  35. Solano F, Briganti S, Picardo M, Ghanem G (2006) Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res 19:550–571

    Article  CAS  PubMed  Google Scholar 

  36. Song K, An SM, Kim M, Koh JS, Boo YC (2011) Comparison of the antimelanogenic effects of p-coumaric acid and its methyl ester and their skin permeabilities. J Dermatol Sci 63:17–22

    Article  CAS  PubMed  Google Scholar 

  37. Spielmann H (2010) The EU commission’s draft report on alternative (Non-animal) methods for cosmetics testing: current status and future prospects–2010: a missed opportunity. Altern Lab Anim 38:339–343

    CAS  PubMed  Google Scholar 

  38. Steinhoff M, Stander S, Seeliger S, Ansel JC, Schmelz M, Luger T (2003) Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol 139:1479–1488

    Article  PubMed  Google Scholar 

  39. Tachibana M (2000) MITF: a stream flowing for pigment cells. Pigment Cell Res 13:230–240

    Article  CAS  PubMed  Google Scholar 

  40. Takara K, Iwasaki H, Ujihara K, Wada K (2008) Human tyrosinase inhibitor in rum distillate wastewater. J Oleo Sci 57:191–196

    Article  CAS  PubMed  Google Scholar 

  41. Takeyama R, Takekoshi S, Nagata H, Osamura RY, Kawana S (2004) Quercetin-induced melanogenesis in a reconstituted three-dimensional human epidermal model. J Mol Histol 35:157–165

    Article  CAS  PubMed  Google Scholar 

  42. Wichers HJ, Recourt K, Hendriks M, Ebbelaar CE, Biancone G, Hoeberichts FA, Mooibroek H, Soler-Rivas C (2003) Cloning, expression and characterisation of two tyrosinase cDNAs from Agaricus bisporus. Appl Microbiol Biotechnol 61:336–341

    Article  CAS  PubMed  Google Scholar 

  43. Wu JM, Hsieh TC (2011) Resveratrol: a cardioprotective substance. Ann N Y Acad Sci 1215:16–21

    Article  CAS  PubMed  Google Scholar 

  44. Yanagihara M, Yoshimatsu M, Inoue A, Kanno T, Tatefuji T, Hashimoto K (2012) Inhibitory effect of gnetin C, a resveratrol dimer from melinjo (Gnetum gnemon), on tyrosinase activity and melanin biosynthesis. Biol Pharm Bull 35:993–996

    Article  CAS  PubMed  Google Scholar 

  45. Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S (1997) Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J Biol Chem 272:503–509

    Article  CAS  PubMed  Google Scholar 

  46. Yoon TJ, Lei TC, Yamaguchi Y, Batzer J, Wolber R, Hearing VJ (2003) Reconstituted 3-dimensional human skin of various ethnic origins as an in vitro model for studies of pigmentation. Anal Biochem 318:260–269

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Korea Health Technology R&D Project of the Ministry of Health & Welfare (Grant No. A103017).

Author information

Authors and Affiliations

  1. Department of Molecular Medicine and Cell and Matrix Research Institute, BK21 plus program, Kyungpook National University School of Medicine, 101 Dongin-dong 2-ga, Jung-gu, Daegu, 700-422, Republic of Korea

    Jiaa Park & Yong Chool Boo

  2. Ruby Crown Co., Ltd, Daegu, Republic of Korea

    Joon Heum Park

  3. Gyeongbuk Natural Color Industry Institute, Gyeongbuk, Republic of Korea

    Hwa-Jin Suh

  4. Department of Cosmetic Science and Technology, Seowon University, Chungbuk, Republic of Korea

    In Chul Lee

  5. Dermapro Skin Research Center, Dermapro Co., Ltd, Seoul, Republic of Korea

    Jaesook Koh

Authors
  1. Jiaa Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joon Heum Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hwa-Jin Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. In Chul Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jaesook Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong Chool Boo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong Chool Boo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Park, J., Park, J.H., Suh, HJ. et al. Effects of resveratrol, oxyresveratrol, and their acetylated derivatives on cellular melanogenesis. Arch Dermatol Res 306, 475–487 (2014). https://doi.org/10.1007/s00403-014-1440-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-014-1440-3

Keywords

search

Navigation