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A study of the human skin-whitening effects of resveratryl triacetate

Archives of Dermatological Research volume 307, pages 239–247 (2015)Cite this article

Abstract

Resveratrol has a variety of bioactivities that include its anti-melanogenic effects, but its use in cosmetics has been challenging partly because of its chemical instability. Resveratryl triacetate (RTA) is a prodrug that can enhance stability. The purpose of this study was to examine the skin safety and whitening effects of RTA in human subjects. The primary skin irritation potentials of RTA and resveratrol were tested at 0.1 and 0.5 % on human subjects. Resveratrol at a concentration of 0.5 % induced weak skin irritation, whereas RTA did not induce any skin responses. The skin-whitening efficacy of a cosmetic formulation containing 0.4 % RTA was evaluated in two different test models. In the artificial tanning model, the test product and the control product were applied twice daily to the skin of the forearms of 22 human subjects after pigmentation induction by ultraviolet irradiation. Applying the test and the control products to the artificial tanning model for 8 weeks increased the individual topology angles (ITA°) by 17.06 and 13.81 %, respectively, a difference that was statistically significant (p < 0.05). In the hyperpigmentation model, the test product and the control product were applied twice daily to the faces of 21 human subjects. The averaged intensity of the hyperpigmented spots decreased by 2.67 % in the test group and 1.46 % in the control group, a difference that was statistically significant (p < 0.05). Therefore, RTA incorporated into cosmetic formulations can whiten human skin without inducing skin irritation.

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References

  1. Aluyen JK, Ton QN, Tran T, Yang AE, Gottlieb HB, Bellanger RA (2012) Resveratrol: potential as anticancer agent. J Diet Suppl 9:45–56

    Article  CAS  PubMed  Google Scholar 

  2. An SM, Ham H, Choi EJ, Shin MK, An SS, Kim HO, Koh JS (2014) Primary irritation index and safety zone of cosmetics: retrospective analysis of skin patch tests in 7,440 Korean women during 12 years. Int J Cosmet Sci 36:62–67

    Article  Google Scholar 

  3. 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 

  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. 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 

  6. Arnau J, Bendayan R, Blanca MJ, Bono R (2013) The effect of skewness and kurtosis on the robustness of linear mixed models. Behav Res Methods. 45:873–879

    Article  PubMed  Google Scholar 

  7. Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL (2009) Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms. Arch Biochem Biophys 486:95–102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Brisson L, Castan S, Fontbonne H, Nicoletti C, Puigserver A, el Ajandouz H (2008) Alpha-tocopheryl acetate is absorbed and hydrolyzed by Caco-2 cells comparative studies with alpha-tocopherol. Chem Phys Lipids 154:33–37

    Article  CAS  PubMed  Google Scholar 

  9. 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 

  10. 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 

  11. 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 

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

    Article  CAS  PubMed  Google Scholar 

  13. Farris P, Krutmann J, Li YH, McDaniel D, Krol Y (2013) Resveratrol: a unique antioxidant offering a multi-mechanistic approach for treating aging skin. J Drugs Dermatol 12:1389–1394

    CAS  PubMed  Google Scholar 

  14. Frosch PJ, Kligman AM (1979) The soap chamber test. A new method for assessing the irritancy of soaps. J Am Acad Dermatol 1:35–41

    Article  CAS  PubMed  Google Scholar 

  15. 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 

  16. 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 

  17. Kulkarni SS, Canto C (2014) The molecular targets of resveratrol. Biochim Biophys Acta. doi:10.1016/j.bbadis.2014.10.005

    PubMed Central  Google Scholar 

  18. 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

    Article  CAS  PubMed  Google Scholar 

  19. Loffler H, Pirker C, Aramaki J, Frosch PJ, Happle R, Effendy I (2001) Evaluation of skin susceptibility to irritancy by routine patch testing with sodium lauryl sulfate. Eur J Dermatol 11:416–419

    CAS  PubMed  Google Scholar 

  20. 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 

  21. 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 

  22. Ogas T, Kondratyuk TP, Pezzuto JM (2013) Resveratrol analogs: promising chemopreventive agents. Ann N Y Acad Sci 1290:21–29

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. Park J, Park JH, Suh HJ, Lee IC, Koh J, Boo YC (2014) Effects of resveratrol, oxyresveratrol, and their acetylated derivatives on cellular melanogenesis. Arch Dermatol Res 306:475–487

    Article  CAS  PubMed  Google Scholar 

  25. 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 

  26. 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 

  27. Pezzuto JM, Kondratyuk TP, Ogas T (2013) Resveratrol derivatives: a patent review (2009–2012). Expert Opin Ther Pat 23:1529–1546

    Article  CAS  PubMed  Google Scholar 

  28. Pierard GE (1998) EEMCO guidance for the assessment of skin colour. J Eur Acad Dermatol Venereol 10:1–11

    CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. 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 

  31. 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 

  32. 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 

  33. 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 

  34. Wattanakrai P, Suwanachote S, Kulkollakarn S, Rajatanavin N (2007) The study of human skin irritation of a novel herbal skin care product and ingredients by human single closed patch testing. J Med Assoc Thai 90:1116–1122

    PubMed  Google Scholar 

  35. Wright DB, Herrington JA (2011) Problematic standard errors and confidence intervals for skewness and kurtosis. Behav Res Methods 43:8–17

    Article  PubMed  Google Scholar 

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

    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 and Welfare (Grant no. HN12C0051).

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    Authors and Affiliations

    1. Dermapro Skin Research Center, Dermapro Ltd., Seoul, Republic of Korea

      Ja Hyun Ryu, Sang Mi An, Ji Hwoon Baek & Jae Sook Koh

    2. Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, 101 Dongin-dong 2-ga, Daegu, Jung-Gu, 700-422, Republic of Korea

      Jin Kyung Seok & Yong Chool Boo

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

      Yong Chool Boo

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    1. Ja Hyun Ryu
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    2. Jin Kyung Seok
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    Correspondence to Yong Chool Boo.

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    J. H. Ryu and J. K. Seok contributed equally.

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    Ryu, J.H., Seok, J.K., An, S.M. et al. A study of the human skin-whitening effects of resveratryl triacetate. Arch Dermatol Res 307, 239–247 (2015). https://doi.org/10.1007/s00403-015-1556-0

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    • DOI: https://doi.org/10.1007/s00403-015-1556-0

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