Topical Application of γ-Tocopherol Derivative Prevents UV-Induced Skin Pigmentation

• Published in: Biological & pharmaceutical bulletin Vol. 29; no. 6; pp. 1175 - 1179
• Main Authors: Kuwabara, Yuka, Watanabe, Tatsuya, Yasuoka, Shingo, Fukui, Kohsuke, Takata, Jiro, Karube, Yoshiharu, Okamoto, Yuko, Asano, Shin, Katoh, Eiko, Tsuzuki, Toshi, Kobayashi, Shizuko
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.06.2006
• Subjects: Administration, Topical; Animals; Cell Line, Tumor; gamma-Tocopherol - administration & dosage; gamma-Tocopherol - analogs & derivatives; gamma-Tocopherol - therapeutic use; Glycine - administration & dosage; Glycine - analogs & derivatives; Glycine - therapeutic use; Guinea Pigs; hyper-pigmentation; Melanins - biosynthesis; melanogenesis; Skin - drug effects; Skin - metabolism; Skin - radiation effects; Skin Pigmentation - drug effects; Skin Pigmentation - radiation effects; tyrosinase; ultraviolet light B; Ultraviolet Rays; γ-tocopherol; γ-tocopheryl-N,N-dimethylglycinate hydrochloride
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.29.1175

We previously reported that a novel hydrophilic γ-tocopherol (γ-Toc) derivative, γ-tocopheryl-N,N-dimethylglycinate hydrochloride (γ-TDMG) gets converted to the antioxidant γ-Toc in skin. We also found that this derivative displayed greater bioavailability than γ-Toc itself. In the present study, we determined whether γ-TDMG could reduce UV-induced skin pigmentation in brownish guinea pigs. γ-TDMG (0.1 or 0.5%) was topically applied to the skin before and after it was exposed to UVB plus UVA (3 times/week for 1 week), and then 10 times/week for 4 weeks thereafter. Treatment with 0.5% γ-TDMG resulted in significant skin lightening (70% of the pigmentation of irradiated controls). We also found that melanin synthesis was dose-dependently inhibited by γ-TDMG in murine B16 melanoma cells. When γ-TDMG or kojic acid (250 μM) were added to homogenates of B16 melanoma cells, their tyrosinase activity was significantly inhibited by approximately 40% and 75%, respectively. Mushroom tyrosinase activity was significantly inhibited by 200 μM γ-Toc and kojic acid, but not γ-TDMG. When B16 cells were incubated with 250 μM γ-TDMG for 24 or 48 h, their intracellular γ-Toc concentrations rose over 100 fold to 10.5 and 11.2 nmol/106 cells, respectively, suggesting that γ-TDMG was rapidly converted to γ-Toc in these cells and that their reduced melanin synthesis may have been due to the activity of γ-Toc. Our data further suggest that the topical application of γ-TDMG may be efficacious in preventing photo-induced skin pigmentation in humans.