Shinya Kasamatsu1, Akira Hachiya2, Shun Nakamura3, Yuka Yasuda3, Taketoshi Fujimori1, Kei Takano1, Shigeru Moriwaki1, Tadashi Hase1, Tamio Suzuki4, Kayoko Matsunaga5. 1. Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan. 2. Biological Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan. Electronic address: hachiya.akira@kao.co.jp. 3. Analytical Science Laboratories, Kao Corporation, Haga 321-3497, Tochigi, Japan. 4. Department of Dermatology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan. 5. Department of Dermatology, Fujita Health University School of Medicine, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan.
Abstract
BACKGROUND: Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol. OBJECTIVE: To investigate the mechanism underlying the depigmentation caused by rhododendrol-containing cosmetics, this study was performed. METHODS: The mechanism above was examined using more than dozen of melanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect rhododendrol and its metabolites in the presence of tyrosinase. RESULTS: Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the rhododendrol-induced melanocyte impairment. Hydroxyl-rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity. CONCLUSION: The generation of a tyrosinase-catalyzed hydroxyl-metabolite is one of the causes for the diminishment of the melanocyte viability by rhododendrol.
BACKGROUND:Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol. OBJECTIVE: To investigate the mechanism underlying the depigmentation caused by rhododendrol-containing cosmetics, this study was performed. METHODS: The mechanism above was examined using more than dozen of melanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect rhododendrol and its metabolites in the presence of tyrosinase. RESULTS: Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the rhododendrol-induced melanocyte impairment. Hydroxyl-rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity. CONCLUSION: The generation of a tyrosinase-catalyzed hydroxyl-metabolite is one of the causes for the diminishment of the melanocyte viability by rhododendrol.