Topical Application of .GAMMA.-Tocopherol Derivative Prevents UV-Induced Skin Pigmentation

Abstract

Melanin plays an important role in preventing ultraviolet (UV) light-induced skin damage. On the other hand, overexposure to UV radiation can lead to a pathological increase in melanin production. Epidermal hyper-pigmentation results from the increased activity of melanogenic enzymes such as tyrosinase. [1][2][3] Tyrosinase oxidizes the conversion of L-tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and DOPA to DOPA quinone, which are the first two rate limiting steps in the melanin synthesis pathway. 3,4) As such, inhibitors of this enzyme suppress melanogenesis in the epidermal layer of skin, a fact that has led to the development of skin-lightening tyrosinase inhibitors by the cosmetics and pharmaceutical companies.4-7) While several melanin-inducing compounds have also been investigated for their possible use as UV protectants, few have actually reached the consumer market because of safety concerns.Data suggest that in addition to tyrosinase, factors released by keratinocytes and/or melanocytes stimulate melanin production by melanocytes. These factors include histamine, 8) a-MSH (melanocyte-stimulating hormone), 9) ET-1 (Endothelin-1), 10) and PGE2 (Prostaglandin E2), 11) which have all been reported to enhance melanin production in response to UV radiation. Nitric oxide (NO) was also suggested to influence skin pigmentation. 12)Tocopherol has four homologs i.e., a, b, g and d which differ in the number and position of methyl groups in their chroman ring. a-Toc is a well known scavenger of reactive oxygen species (ROS) such as hydroxyradical.13) a-tocopherol (a-Toc) was reported to be an effective treatment for facial hyperpigmentation.14,15) More recently, g-Toc and its metabolite g-carboxyethyl hydroxychroman (g-CEHC) were found to be natriuretic factors, [16][17][18] to inhibit prostate cancer cell proliferation [19][20][21][22] and the activity of the proinflammatory enzyme cyclooxygenase-2, [23][24][25] and to scavenge peroxyl radicals and peroxynitrite.26-28) g-Toc was also found to suppress the expression of tyrosinase and tyrosinase related protein-2 in B16 melanoma cells. 29)g-Toc is nearly insoluble in water and is readily oxidized by atmospheric oxygen. The phenolic functional group in gToc is easily esterified and some of its ester derivatives have shown improved water-solubility and resistance to oxidation. Tocopheryl-dimethyl-glycinate (TDMG) is a novel Toc derivative developed by Takata et al. 30) in which dimethylglycine is ester-linked to the sixth position of the chromanoxyl ring of Toc. We previously reported that the chromanoxyl ring of g-TDMG scavenges ROS generated by ultraviolet rays and that it exhibited greater bioavailability than g-Toc in mouse skin. 31)In this study, we examined whether the topical application of g-TDMG could reduce UV-induced hyper-pigmentation of the skin. We also examined its mechanism of action and compared it to that of the fungal metabolic product kojic acid, which is a skin-lightening agent. MATERIALS AND METHODSChemicals g-TDMG and g-Toc were kindly supp...

Skin-Lightening Effect of a Polyphenol Extract from Acerola (Malpighia emarginataDC.) Fruit on UV-Induced Pigmentation

“…A direct effect of UV photons on DNA results in upregulation of the gene for tyrosinase, this then leading to epidermal hyper-pigmentation. [1][2][3] Tyrosinase oxidizes the conversion of L-tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and of DOPA to DOPA quinone, these being the first two rate-limiting steps on the melanin synthesis pathway. 2,4) UV radiation also induces the formation of reactive oxygen species (ROS) in the skin; these ROS contribute to melanin biosynthesis and DNA damage and may then induce the proliferation and/or apoptosis of melanocytes.…”

Effects of Red Ginseng extract on ultraviolet B‐irradiated skin change in C57BL mice

“…It was found that Red Ginseng extract (20 or 60 mg/kg, twice daily) prevented increased production of melanin. It has been reported that ascorbic acid derivatives and γ-tocopherol derivatives decreased UVB-induced skin hyper-pigmentation and melanin levels through their antioxidative properties (Kuwabara et al, 2006;Ochiai et al, 2006). Im et al (2003) reported that Ginseng radix inhibited tyrosinase activity and decreased melanin content and cell proliferation in B16 melanoma cells (in vitro).…”

Antioxidant Defense and UV-Induced Melanogenesis: Implications for Melanoma Prevention

“…Hydrophilic γ-tocotrienol reduced UV-induced pigmentation in guinea pig skin via inhibition of tyrosinase activity (Kuwabara et al, 2006). Tocotrienols inhibited UVB-induced melanogenesis in different melanoma cells through downregulation of tyrosinase activity and protein (Yap et al, 2010).…”