Skin-lightening products revisited.

[en] Skin colour typology depends on the amount and location of its chromophores. Among them, eumelanins derived from 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI), and phaeomelanins are of utmost importance. These biomolecules result from the multi-step enzymatic and non-enzymatic conversion of tyrosine into melanins. Pigmentation disorders are multiple and depend on alterations in the density in active melanocytes, and on specific abnormalities of any of the complex melanogenesis mechanisms. This review presents some of the main skin-lightening agents with respect to their mechanisms of action and side-effects. Some of the novel compounds may lead to new perspectives in the fields of dermatology and cosmetology. The methods commonly used to assess efficacy of skin-lightening products rely on in vitro models including cell-free enzymatic assays, melanocyte cultures and reconstructed epidermis bioassays. Animal models have little relevance. By contrast, human testing with the support of instrumental evaluations is the most informative.

Disciplines :

Dermatology

Author, co-author :

Petit, Ludivine; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie

Pierard, Gérald ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie

Language :

English

Title :

Skin-lightening products revisited.

Publication date :

2003

Journal title :

International Journal of Cosmetic Science

ISSN :

0142-5463

eISSN :

1468-2494

Publisher :

Blackwell Publishing, United Kingdom

Volume :

Issue :

Pages :

169-81

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 12 March 2009

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Bibliography

Andersen, P.H. and Bjerring, P. Noninvasive computerized analysis of skin chromophores in vivo by reflectance spectroscopy. Photodermatol. Photoimmunol. Photomed. 7, 249-257 (1990).
Piérard, G.E. EEMCO guidance for the assessment of skin color. J. Eur. Acad. Dermatol. Vener. 10, 1-11 (1998).
Hearing, V.J. Biochemical control of melanogenesis and melanosomal organization. J. Invest. Dermatol. Symp. Proc. 4, 24-28 (1999).
Ortonne, J.P. and Ballotti, R. Melanocyte biology and melanogenesis what's new? J. Dermatol. Treat. 11, S15-S26 (2000).
Seiberg, M., Paine, C., Shadow, E. et al. The protease-activated receptor 2 regulates pigmentation via keratinocyte-melanocyte interactions. Exp. Cell. Res. 254, 25-32 (2000).
Piérard, G.E., Piérard-Franchimont, C., Laso Dosal, F. et al. Pigmentary changes in skin senescence. J. Appl. Cosmetol. 9, 57-63 (1991).
Castanet, J. and Ortonne, J.P. Pigmentary changes in aged and photoaged skin. Arch. Dermatol. 133, 1296-1299 (1997).
Hermanns, J.F., Petit, L., Piérard-Franchimont, C. et al. Unravelling the patterns of subclinical phaeomelanin-enriched facial hyperpigmentation, effect of depigmenting agents. Dermatology 202, 118-122 (2000).
Petit, L., Fogouang, L., Uhoda, I. et al. Regional variability in mottled photo-induced melanoderma in the elderly. Exp. Gerontol. 38, 327-331 (2003).
Ando, H., Itoh, A., Mishima, Y. and Ichihashi, M. Correlation between the number of melanosomes, tyrosinase mRNA levels, and tyrosinase activity in cultured murine melanoma cell in response to various melanogenesis regulatory agents. J. Cell Physiol. 163, 608-614 (1995).
Dooley, T.P. Topical skin depigmentation agents, current products and discovery of a novel inhibitor of melanogenesis. J. Dermatol. Treat. 8, 275-279 (1997).
Kasraee, B. Peroxidase-mediated mechanisms are involved in the melanocytotoxic and melanogenesis-inhibiting effects of chemical agents. Dermatology 205, 329-339 (2002).
Seiberg, M., Paine, C., Sharlow, E. et al. Inhibition of melanosome transfer results in skin lightening. J. Invest. Dermatol. 115, 162-167 (2000).
Paine, C., Sharlow, E., Liebel, F. et al. An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway. J. Invest. Dermatol. 116, 587-595 (2001).
Cotellessa, C., Peris, K., Onorati, M.T. et al. The use of chemical peelings in the treatment of different cutaneous hyperpigmetations. Dermatol. Surg. 25, 450-454 (1999).
Chakraborty, A., Slominski, A., Ermak, G. et al. Ultraviolet B and melanocyte-stimulating hormone (MSH) stimulate mRNA production for αMSH receptors and proopiomelanocortin-derived peptides in mouse melanoma cells and transformed keratinocytes. J. Invest. Dermatol. 105, 655-659 (1995).
Funasaka, Y., Chakraborty, A.K., Hayashi, Y. et al. Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes, evidence for a regulatory role of ultraviolet B, interleukin-1α, interleukin-1β, endothelin-1 and tumor necrosis factor-α. Br. J. Dermatol. 139, 216-224 (1998).
Suzuki, I., Im. S., Tada, A. et al. Participation of the melanocortin-1 receptor in the UV control of pigmentation. J. Invest. Dermatol. Symp. Proc. 4, 329-344 (1999).
Tanaka, Y. and Masuda, M. Trends in skin-whitening agents in Japan. Oleochemicals 9, 306-314 (1998).
Morelli, J.G. and Norris, D.A. Influence of inflammatory mediators and cytokines on human melanocyte function. J. Invest. Dermatol. 100, 191S-195S (1993).
Tada, A., Suzuki, I., Im, S. et al. Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation. Cell Growth Diff. 9, 575-584 (1998).
Bertolotto, C. and Ballotti, R. La tyrosinase est l'enzyme clé de la mélanogenèse. Cosmétologie 24, 20-22 (1999).
Schauer, E., Trautinger, F., Köck, A. et al. Proopiomelanocortin- derived peptides are synthesized released human keratinocytes. J. Clin. Invest. 93, 2258-2262 (1994).
Böhm, M. and Luger, T.A. The role of melanocortins in skin homeostasis. Horm. Res. 54, 287-293 (2000).
Suzuki, I., Cone, R.D., Im, S. et al. Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology 137, 1627-1633 (1996).
Abdel-Malek, Z., Scott, M.C., Suzuki, I. et al. The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation. Pigment Cell Res. 13 (Suppl. 8), 156S-1562S (2000).
Suzuki, I.,Tada, A., Ollmann, M.M. et al. Agouti signaling protein inhibits melanogenesis and the response of human melanocytes to α-melanotropin. J. Invest. Dermatol. 108, 838-842 (1997).
Furumura, M., Sakai, C. and Abdel-Malek, Z. The interaction of agouti signal protein and melanocyte stimulating hormone to regulate melanin formation in mammals. Pigment Cell Res. 9, 191-203 (1996).
Yoshida, M., Takahashi, Y. and Inoue, S. Histamine induces melanogenesis and morphologic changes by protein kinase A activation via H2 receptors in human normal melanocytes. J. Invest. Dermatol. 114, 334-342 (2000).
Roméro-Graillet, C., Aberdam, E., Clément, M. et al. Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis. J. Clin. Invest. 99, 635-642 (1997).
Ando, H., Oka, M., Mishima, Y. and Ichihashi, M. Protein kinase C and linoleic acid-induced inhibition of melanogenesis. Pigment Cell Res. 3, 2000-2006 (1990).
Ando, H., Funasaka, Y., Oka, M. et al. Possible involvement of proteolytic degradation of tyrosinase in the regulatory effect of fatty acids on melanogenesis. J. Lipid Res. 40, 1312-1316 (1999).
Montastier, C., Nguyen, Q.L. and Giacomoni, P. Méthodes d'objectivation des effets des agents dépigmentants chez l'homme. J. Med. Esthet. Chir. Dermatol. 22, 93-103 (1995).
Virador, V.M., Kobayashi, N., Matsunaga, J. et al. A standardized protocol for assessing regulators of pigmentation. Anal. Biochem. 270, 207-219 (1999).
Madhosingh, C. and Sundberg, L. Purification and properties of tyrosinase inhibitor from mushrooms. FEBS Lett. 49, 156-158 (1974).
Schmidt, R., Krien, P. and Régnier, M. The use of diethylaminoethyl-cellulose membrane filters in a bioassay to quantify melanin synthesis. Anal. Biochem. 235, 113-118 (1996).
Bessou, S., Pain, C. and Taïeb, A. Use of pigment skin reconstructs in the study of pigment modifiers. Arch. Dermatol. 133, 331-336 (1997).
Régnier, M., Duval, C., Galey, J.B. et al. Keratinocyte- melanocyte co-cultures and pigmented reconstructed human epidermis, models to study modulation of melanogenesis. Cell. Mol. Biol. 45, 969-980 (1999).
Fullerton, A., Fischer, T., Lahti, A. et al. Guidelines for measurement of skin colour and erythema. Contact Dermatitis 31, 1-10 (1996).
Hermanns, J.F., Piérard-Franchimont, C. and Piérard, G.E. Skin colour assessment in safety testing of cosmetics. An overview. Int. J. Cosmet. Sci. 22, 67-71 (2000).
Hermanns, J.F., Petit, L., Hermanns-Lê,T. and-Piérard, G.E. Analytic quantification of phototype-related regional skin complexion. Skin Res. Technol. 7, 168-171 (2001).
Takiwaki, H., Overgaard, L. and Serup, J. Comparison of narrow-band reflectance spectrophotometric and tristimulus colorimetric measurements of skin color. Skin Pharmacol. 7, 217-225 (1994).
Geyer, A., Vilser, W., Karte, K. and Wollina, U. Remittance spectroscopy of human skin in vivo. Skin Res. Technol. 2, 122-125 (1996).
Piérard, G.E. Narrow-band spectrophotometry and tristimulus colorimetry for the assessment of skin colour. Gior. Int. Dermatol. Ped. 8, 193-196 (1996).
Karamfilov, Th., Weichold, S., Karte, K. et al. Remittance spectroscopy mapping of human skin in vivo. Skin Res. Technol. 5, 49-52 (1999).
Liebold, K., Fassler, D., Schmidt, W.D. et al. In vivo spectroscopy in dermatology, methods and new fields of application. J. Eur. Acad. Dermatol. Vener. 14, 1-4 (2000).
Chardon, A., Cretois, I. and Hourseau, C. Skin colour typology and suntanning pathways. Int. J. Cosmet. Sci. 13, 191-208 (1991).
Kollias, N., Gillies, R., Cohen-Goihman, C., Phillips, S.B. et al. Fluorescence photography in the evaluation of hyperpigmentation in photodamaged skin. J. Am. Acad. Dermatol. 36, 226-230 (1997).
Hermanns, J.F., Petit, L., Piérard-Franchimont, C. et al. Assessment of topical hypopigmenting agents on solar lentigines of Asian women. Dermatology 204, 281-286 (2002).
Petit, L. and Piérard, G.E. Analytic quantification of solar lentigines lightening by a 2% hydroquinone-cyclodextrin formulation. J. Eur. Acad. Dermatol. Vener. (in press).
Fitzpatrick, T.B. The validity and practicality of sunreactive skin types I through VI. Arch. Dermatol. 124, 869-871 (1988).
Miyamoto, K., Takiwaki, H., Hillebrand, G. et al. Utilization of a high-resolution digital imaging system for the objective and quantitative assessment of hyperpigmented spots on the face. Skin Res. Technol. 8, 73-77 (2002).
Miyamoto, K., Takiwaki, H., Hillebrand, G.G. and Arase, S. Development of a digital imaging system for objective measurement off hyperpigmented spots on the face. Skin Res. Technol. 8, 227-235 (2002).
Piérard-Franchimont, C. and Piérard, G.E. Assessment of aging and actinic damages by cyanoacrylate skin surface strippings. Am. J. Dermatopathol. 9, 500-509 (1987).
Jimbow, K. and Minamitsuji, Y. Topical therapies for melasma and disorders of hyperpigmentation. Dermatol. Ther. 14, 35-45 (2001).
Kligman, A.M. and Willis, I. A new formula for depigmenting human skin. Arch. Dermatol. 111, 40-48 (1975).
Garcia, A. and Fulton, J.E. The combination of glycolic acid and hydroquinone or kojic acid for the treatment of melasma and related conditions. Dermatol. Surg. 22, 443-447 (1996).
Lim, J.T.E. Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid. Dermatol. Surg. 25, 282-284 (1999).
Ferioli, V., Rustichelli, C. Pavesi, G. and Gamberini, G. New combined treatment of hypermelanosis, analytical studies on efficacy and stability improvement. Int. J. Cosmet. Sci. 23, 333-340 (2001).
Wester, R.C., Melendres, J., Hui, X. et al. Human in vivo and in vitro hydroquinone topical bioavailability, metabolism and disposition. J. Toxicol. Environ. Health 54, 301-317 (1998).
Smith, C.J., O'Hare, K.B. and Allen, J.C. Selective cytotoxicity of hydroquinone for melanocyte-derived cells is mediated by tyrosinase activity but independent of melanin content. Pigment Cell Res. 1, 386-389 (1988).
Palumb, A., Dischia, M. and Misuraca, G. Mechanism of inhibition of melanogenesis by hydroquinone. Biochem. Biophys. Acta 1073, 85-90 (1991).
Bolognia. J.L., Sodi, S.A., Osber, M.P. and Pawelek, J.M. Enhancement of the depigmenting effect of hydroquinone by cystamine and buthionine sulfoximine. Br. J. Dermatol. 133, 349-357 (1995).
De Caprio, A.P. The toxicology of hydroquinone-relevance to occupational and environmental exposure. Crit. Rev. Toxicol. 29, 283-230 (1999).
Hoshow, R.A., Zimmerman, K.G. and Menter, A. Ochronosis-like pigmentation from hydroquinone bleaching creams in American Blacks. Arch. Dermatol. 121, 105-108 (1985).
Piérard-Franchimont, C. and Piérard, G.E. Pigmentation induite par l'hydroquinone. Nouv. Dermatol. 8, 234-236 (1986).
Hardwick, N., van Gelder, L.W., van der Merwe, C.A et al. Exogenous ochronosis, an epidemiological study. Br. J. Dermatol. 120, 229-238 (1989).
Markey, A.C., Black, A.K. and Rycroft, R.J. Confetti-like pigmentation from hydroquinone. Contact Dermatitis 20, 148-149 (1989).
Levin, C.Y. and Maibach, H. Exogenous ochronosis. An update on clinical features, causative agents and treatment options. Am. J. Clin. Dermatol. 2, 213-217 (2001).
Ortonne J.P., Bahadoran P., Fitzpatrick, T.B., Mosher, D.B. and Hori, Y. Hypomelanoses and hypermelanoses. In: Dermatology in General Medicine (I. M. Freedberg, A. Z. Eisen, K. Wolff, K. F. Austin, L. A. Goldsmith and S. I. Katz, eds), 6th edn, pp. 836-880. McGraw-Hill, New York (2003).
Riley, P.A. Mechanism of pigment cell toxicity produced by hydroxyanisole. J. Pathol. 101, 163-169 (1970).
Naish-Byfleld, S., Cooksey, C.J., Later, A.M., Johnson, C.I. and Riley, P.A. In vitro assessment of the structure activity relationship of tyrosinase dependent cytotoxicity of a series of substituted phenols. Melanoma Res. 1, 273-287 (1991).
Nair, X., Parab, P., Suhr, L. andTramposch, K.M. Combination of 4-hydroxyanisole and all-trans-retinoic acid produces synergistic skin depigmentation in swine. J. Invest Dermatol. 101, 145-149 (1993).
Fleisher, A.B., Schwartzel, E.H., Colby, S.I. et al. The combination of 2% 4-hyroxyanisole (mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented spots in two double-blind multicenter clinical studies. J. Am. Acad. Dermatol. 42, 459-467 (2000).
Kasraee, B., Handjani, F. and Aslani, F.S. Enhancement of the depigmenting effect of hydroquinone and 4-hydroxyanisole by all-trans-retinoic acid (tretinoin): the impairment of glutathione-dependent cytoprotection? Dermatology 206, 289-291 (2003).
Maeda, K. and Fukuda, M. Arbutin, mechanism of its depigmenting action in human melanocyte culture. J. Pharmacol. Exp. Ther. 276, 765-769 (1996).
Kanwar, A.J., Dhar, S. and Kaur, S. Treatment of melasma with potent topical corticosteroids. Dermatology 188, 170 (1994).
Mahé, A., Keita, S. and Bobin. P. Complications dermatologiques de l'utilisation cosmétique de produits dépigmentants à Bamako (Mali). Ann. Dermatol. Venereol. 121, 142-146 (1994).
Raynaud, E., Cellier, C. and Perret, J.L. Dépigmentation cutanée à visée cosmétique. Enquête de prévalence et effets indésirables, dans une population féminine sénégalaise. Ann. Dermatol. Venereol. 128, 720-724 (2001).
Pathak, M.A., Fitzpatrick, T.B. and Icraus, E.W. Usefulness of retinoic acid in the treatment of melasma. J. Am. Acad. Dermatol. 15, 894-899 (1986).
Griffiths, C.E.M., Finkel, L.J., Ditre, C.M. et al. Topical tretinoin (retinoic acid) improves melasma, a vehicle-controlled clinical trial. Br. J. Dermatol. 129, 415-421 (1993).
Kimbrough-Green, C.K., Griffiths, C.E.M., Finkel, L.J. et al. Topical retinoic acid (tretinoin) for melasma in black patients. Arch. Dermatol, 130, 727-733 (1994).
Pérez-Bernal, A., Munoz-Pérez, M.A. and Camacho, F. Management of facial hyperpigmentation. Am. J. Clin. Dermatol. 1, 261-268 (2001).
Kulkarni, A.A. and Kulkarni, A.P. Retinoids inhibit mammalian glutathione transferases. Cancer Lett. 91, 185-189 (1995).
Xia, C., Taylor, J.B., Spencer, S.R. and Ketterer, B. The human glutathione S-transferase P1-1 gene: modulation of expression by retinoic acid and insulin. Biochem. J. 292, 845-850 (1993).
Duteil, L. and Ortonne, J.P. Colorimetric assessment of the effects of azelaic acid on light-induced skin pigmentation. Photodermat. Photoimmun. Photomed. 9, 67-71 (1992).
Breathnach, A. S. Pharmacological properties of azelaic acid, a rationale for clinical use. Clin. Drug Invest. 10 (Suppl. 2). 27-33 (1995).
Sivayathorn, A., Verralo-Rowell, V. and Graupe, K. 20% azelaic acid cream in the topical treatment of melasma, a double-blind comparison with 2% hydroquinone. Eur. J. Dermatol 5, 680-684 (1995).
Lowe, N.J., Rizk, D., Grimes, P. et al. Azelaic acid 20% cream in the treatment of facial hyperpigmentation in darker-skinned patients. Clin. Ther. 20, 945-959 (1998).
Sarkar, R., Bhalla, M. and Kanwar, A.J. A comparative study of 20% azelaic acid cream monotherapy versus a sequential therapy in the treatment of melasma in dark-skinned patients. Dermatology 205, 249-254 (2002).
Kakita, L.S. and Lowe, N.J. Azelaic acid and glycolic acid combination therapy for facial hyperpigmentation in darker-skinned patients, a clinical comparison with hydroquinone. Clin. Ther. 20, 960-970 (1998).
Cabanes, J., Chazzarra, S. and Garcia-Carmona, F. Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase. J. Pharm. Pharmacol. 46, 982-985 (1994).
Lim, J.T. Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid. Dermatol. Surg. 25, 282-284 (1999).
Masse, M.O., Duvallet, V. and Borremans, M. Identification and quantitative analysis of kojic acid and arbutine in skin-whitening cosmetics. Int. Cosmet. Sci. 23, 219-232 (2001).
Ros, J.R., Rodriguez-Lopes, J.N. and Garcia-Canovas, F. Effect of L-ascorbic acid on the monophenolase activity of tyrosinase. Biochem. J. 295, 309-312 (1993).
Kameyama, K., Sakai, C., Kondoh, S. et al. Inhibitory effect of magnesium 1-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and invivo. J. Am. Acad. Dermatol. 34, 29-33 (1996).
Morganti, P., Fabrizi, G., Morganti, G. and Guarneri, F. A new cosmeceutical with a skin lightening activity, second note. The combining whitening activity of a hydrosoluble and a liposoluble vitamin C derivative. SOFW J. 128, 23-25 (2002).
Nomura, H., Ishiguro, T. and Morimoto, S. Studies on L-ascorbic acid derivatives. Part II. L-Ascorbic acid and 3-phosphate and 3-pyrophosphate. Chem. Pharm. Bull. (Tokyo) 17, 381-386 (1989).
Huh, C.H., Seo, K.I., Park, J.Y., Lim, J.G., Eun, H.C. and Park, K.C. A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma. Dermatology 206, 316-320 (2003).
Hakozaki, T., Minwalla, L., Zhuang, J. et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br. J. Dermatol. 147, 20-31 (2002).
Okubo, T., Oyobikawa, M., Futaki, H. et al The inhibitory effects of 4-N-butyl-resorcinol on melanogenesis. J. Dermatol. Sci. 10, 88-92 (1995).
Tsai, T.F., Paul, B.H., Jee, S.H. et al. Effects of glycolic acid on light-induced skin pigmentation in Asian and Caucasian subjects. J. Am. Acad. Dermatol. 43, 238-243 (2000).
Grimes, P.E. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol. Surg. 25, 18-22 (1999).
Pandya, A.G. and Guevara, I.L. Disorders of hyperpigmentation. Dermatol, Clin. 18, 91-98 (2000).
Kubo, I., Kinst-Hori, I. and Yokokawa, Y. Tyrosinase inhibitors for Anacardium occidentale fruits, J. Nat. Prod. 57, 545-551 (1994).
Shimogaki, H., Tanaka, Y., Tamai, H. and Masuda, M. In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition. Int. J. Cosmet. Sci. 22, 291-303 (2000).
Shin, N.H., Ryu, S.Y., Choi, E.J. et al. Oxyresveratrol as the potent inhibitor on dopa oxidase activity of mushroom tyrosinase. Biochem. Biophys. Res. Commun. 243, 801-803 (1998).
Bernard, P. and Berthon, J.Y. Resveratrol, an original mechanism on tyrosinase inhibition. Int. J. Cosmet. Sci. 22, 219-226 (2000).
Hoshino, T., Naru, E., Koide, C. et al. Effects of kojic acid and oil-soluble licorice extract on melanogenesis. J. Soc. Cosmet. Chem. Japan 32, 153-159 (1998).
Yokota, T., Nishio, H., Kubota, Y. et al. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation, Pigment Cell Res. 11, 355-361 (1998).
Nishioka, K. and Seguchi, T. Contact allergy due to oil soluble licorice extracts in cosmetics products. Contact Dermat. 40, 56 (1999).
Ando, H., Ryu, A., Hashimoto, A. et al. Linoleic acid and α-linoleic acid lightens ultraviolet-induced hyperpigmentation of the skin. Arch. Dermatol. Res. 290, 375-381 (1998).