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CHAPTER 33 DEPIGMENTING AGENTS
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FIGURE 33-15 The chemical structure of vitamin E ( -tocopherol, -T)
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FIGURE 33-16 The chemical structure of EGCG
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when used in combination with traditional sunscreens118,119 In a recent study, EGCG was shown to exhibit antiproliferative and proapoptotic effects on human melanoma cells120 No et al examined the tyrosinase inhibitory activity of mushroom tyrosinase in 10 varieties of Korean traditional teas Of the four major polyphenolic catechins, ECG, GCG, and EGCG proved to be the strongest inhibitors of all Of these three, GCG showed the strongest inhibitory effect on tyrosinase, competitively inhibiting the enzyme at its active site121 Furthermore, EGCG was demonstrated to inhibit melanin synthesis in a concentration-dependent manner, not by cell cytotoxicity but by reducing MITF and tyrosinase protein levels in Mel-Ab cells (a mouse-derived spontaneously immortalized melanocyte cell line that produces large amounts of melanin) EGCG displayed a stronger hypopigmenting effect than kojic acid Additionally, EGCG inhibited mushroom tyrosinase activity and, to a lesser degree, human tyrosinase122 Studies of GTPs in human skin have been limited in comparison to animal studies There are two major challenges for the topical use in humans: (1) establishing a standard formulation and delivery systems that ensure the stability of these easily oxidized antioxidants and (2) increasing epidermal penetration of these hydrophilic agents into human skin
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02% pycnogenol Researchers concluded that topical pycnogenol displays potential as a photoprotective complement to sunscreens, clearly evincing biologic activity when applied after UV exposure96 More data are needed to determine the validity of these claims
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Silymarin is a naturally-occurring polyphenolic flavonoid or flavonolignans compound derived from the seeds of the milk thistle plant Silybum marianum126 Milk thistle has been used for medicinal purposes for more than 2000 years Today, it is used clinically in Europe and Asia as an antihepatotoxic agent and is available as a supplement in Europe and the United States The main component of silymarin is silybin (silibinin), which is considered to be its most biologically active constituent in terms of its antioxidant, anti-inflammatory, and anticarcinogenic properties91 Topical application of silybin prior to, or immediately after, UV irradiation has been found to impart strong protection against UV-induced damage in the epidermis by a reduction in thymine dimer-positive cells and an upregulation of p53-p21/Cip1, which researchers believe may lead to the inhibition of cell proliferation and apoptosis This study suggests that mechanisms other than sunscreen effect are integral to silybin efficacy against UV-caused skin damage127 Investigators have also noted that silybin enhances UVB-induced apoptosis and speculated that it acts as a UVB damage sensor to confer its biologic action128 The antioxidant activity of silymarin is well established Chemoprotective activity against skin cancer has also been reported and continues to be the subject of much investigation129,130 In a study to identify the mechanism of photocarcinogenesis prevention in mouse skin by the topical treatment of silymarin, prevention of UVB-induced immunosuppression and oxidative stress were found to be potentially related to the prevention of photocarcinogenesis in mice131 The authors concluded from this trial and related data from other recent studies that there are compelling arguments for the inclusion of silymarin in sunscreens or in other products in a skin care regimen Furthermore, silymarin has been shown to inhibit UV-induced NF- B activation in keratinocytes Researchers have hypothesized that the inhibition of NF- B activation and the consequent inhibition
of UV-induced inflammation by silymarin is a result primarily of the inhibition of UV-induced inflammation by free radical scavenging and a modulation of intracellular GSH content132 Most of the milk thistle or silymarin available in the United States comes in the form of oral supplements The extant evidence on this botanical suggests potent antioxidant strength and great potential as an antiphotodamage, anticarcinogenic component in an improved medical, dermatologic armamentarium Moreover, silymarin may favorably supplement sunscreen protection and provide additional antiphotocarcinogenic protection133
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