ijms International Journal of Molecular Sciences Int. J. Mol. Sci. 1422-0067 Molecular Diversity Preservation International (MDPI) 10.3390/ijms11072699 ijms-11-02699 Addendum Quasi-Drugs Developed in Japan for the Prevention or Treatment of Hyperpigmentary Disorders. Int. J. Mol. Sci. 2010, 11, 2566–2575 AndoHideya12* MatsuiMary S.3 IchihashiMasamitsu12 Skin Aging and Photo-aging Research Center, Doshisha University, Kizugawa, Kyoto 619-0225, Japan; E-Mail: mm_ichihashi@hotmail.com Kobe Skin Research Institute, Kobe, Hyogo 650-0047, Japan Biological Research Division, The Estee Lauder Companies Inc., Melville, New York 11747, NY, USA; E-Mail: mmatsui@Estee.com Author to whom correspondence should be addressed; E-Mail: hideyaando@aol.com; Tel.: +81-78-304-5791; Fax: +81-78-304-5792. 2010 12 7 2010 11 7 2699 2700 5 7 2010 8 7 2010 © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. 2010

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One additional skin lightening or whitening quasi-drug (QD) has been developed and officially approved by the Ministry of Health, Labor and Welfare of Japan. The active ingredient niacinamide should be included in this review [1]. Its mechanism of skin lightening is based on the inhibition of melanosome transfer from melanocytes to keratinocytes. Niacinamide is listed in Table 1, which classifies compounds according to the mechanism of skin lightening QDs registered in Japan.

Niacinamide (Obtained by Procter & Gamble Company in 2007)

Niacinamide (also termed nicotinamide), a derivative of vitamin B3, has been shown to act as an anti-inflammatory agent in acne [2]. Niacinamide had no effect on the tyrosinase activity and melanin synthesis of cultured normal human melanocytes, however, it was found that niacinamide significantly decreased hyperpigmentation, such as melasma and solar lentigines, via inhibition of melanosome transfer from melanocytes to keratinocytes [3,4].

 References AndoHMatsuiMSIchihashiMQuasi-drugs developed in Japan for the prevention or treatment of hyperpigmentary disordersInt. J. Mol. Sci2010112566257510.3390/ijms1106256620640168 ShalitaARSmithJGParishLHSofmanMSChalkerDKTopical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgarisInt. J. Dermatol19953443443710.1111/j.1365-4362.1995.tb04449.x7657446 HakozakiTMinwallaLZhuangJChhoaMMatsubaraAMiyamotoKGreatensAHillebrandGGBissettDLBoissyREThe effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transferBr. J. Dermatol2002147203110.1046/j.1365-2133.2002.04834.x12100180 GreatensAHakozakiTKoshofferAEpsteinHSchwembergerSBabcockGBissettDTakiwakiHAraseSWickettRRBoissyREEffective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversibleExp. Dermatol20051449850810.1111/j.0906-6705.2005.00309.x15946237 Table

Mechanistic classification of skin lightening QDs approved by the MHLW of Japan.

Target Mechanism Detail Skin Lightening QD
Melanocyte Inhibition of tyrosinase activity Anti-oxidation Ascorbic acid/derivatives
Chelating copper atoms Kojic acid Ellagic acid
Competitive inhibition Arbutin 4MSK Rucinol® 4-HPB
Decrease of tyrosinase protein level Acceleration of Tyr degradation Linoleic acid
Inhibition of Tyr maturation Magnolignan®
Keratinocyte Inhibition of KC-MC signaling Inhibition of UV inflammation Chamomilla extract Tranexamic acid/derivative
Melanocyte and Keratinocyte Inhibition of melanosome transfer Inhibition of melanin dispersion Niacinamide
Epidermis Acceleration of epidermal turnover Desquamation of melanin Placental extract Adenosine mono-phosphate

KC: keratinocyte; MC: melanocyte; Tyr: tyrosinase; UV: ultraviolet light.