SKIN-LIGHTENING COSMETIC INGREDIENTS 49 Most of the natural extracts contain fl avanoids that provide antioxidant effects and are thus used as skin-lightening agents (69). (iv) Vitamins as skin-lightening agents. Vitamins have been known to improve skin tone and texture, and they have found remarkable acceptance among consumers. Most of the lead- ing brands of skin-lightening agents that are available commercially utilize vitamins or their derivatives as ingredients. VITAMIN A. Vitamin A has been used for some decades for the removal of spots in Kligman’s treatment (70). It is used along with hydroquinone and topical steroids for the treatment of melasma. Tretinoin acts as a skin-lightening agent by inducing exfoliation. Further, it accelerates the loss of epidermal melanin by increasing the turnover rate and by promoting the proliferation of keratinocytes (71,72). However, users of tretinoin suffer from side effects such as burning and increased photosensitization. Retinyl palmitate, a derivative of retinoic acid, is used in skin-lightening cosmetic preparations. VITAMIN B. Among the classes of vitamins that comprise vitamin B, two have been identi- fi ed to have skin-lightening activity: (a) Vitamin B3 (niacinamide): This is one of the most used hypopigmenting agents. It is a well known antioxidant and interferes in melanasome transfer leading to skin lightening. Using co-cultures of human melanocytes and keratinocytes, investiga- tors have shown that niacinamide inhibits the transfer of melanosomes from mela- nocytes to keratinocytes (73). The results of clinical studies using topically applied niacin amide have demonstrated a reversible reduction in hyperpigmented lesions and increased skin lightness compared with the vehicle alone after four weeks of use (74). (b) Vitamin B5 (panthenoic acid): A derivative of vitamin B5, calcium pantetheine sulfonate has been observed to interfere with the glycosylation of tyrosinase, thereby leading to depigmenting effects (75). VITAMIN C. Vitamin C is required for the production of collagen and is a photoprotectant as it deactivates UV-induced free radicals and decreases erythema. Further, Vitamin C also acts as a tyrosinase inhibitor, thereby lightening the skin (76). Although most effective, ascorbic acid is a highly unstable compound. Stable derivatives of ascorbic acid in the Figure 4. Structures of (a) glutathione and (b) phytic acid.

JOURNAL OF COSMETIC SCIENCE 50 form of sodium ascorbyl phosphate (SAP), magnesium ascorbyl phosphate (MAP), and ascorbyl palmitate are widely used in cosmetic products (77). VITAMIN E. Vitamin E is the most important lipid-soluble antioxidant in the body. It is abundant in the sebum and acts to absorb the oxidative stress of sunlight and skin expo- sure. It has been demonstrated that vitamin E provides protection against UV-induced infl ammation and hyperpigmentation (78). Vitamin E has also been studied in combina- tion therapies with other vitamins as well as in other classes of skin-lightening com- pounds (79,80). Vitamins B, C, and E are used individually or in combination in many skin-lightening treatment therapies. (v) Peptides in skin lightening. Peptides are reported to reduce pigmentation through inter- action with the protease-activated receptor 2 (PAR-2) of keratinocytes. PAR-2 activation in involved in cell growth, differentiation, and infl ammatory processes and was shown to affect melanin and melanosome ingestion by human keratinocytes (81). The protease- activated receptor-2 upregulates keratinocyte phagocytosis. The peptide-based antago- nist for PAR-2 can be used to regulate melanin ingestion by keratinocytes, thus effecting skin-lightening. Short peptides have also been reported in reducing the enzymatic activity of tyrosinase (82). The use of sericin, a high-molecular-weight soluble glycoprotein from silk, as a tyrosinase inhibitor has also been documented (83). Peptide residues that act as MSH inhibitors have been known to lighten the skin. Soy trypsin inhibitors have been identi- fi ed as interfering in melanosomal transfer, thereby reducing skin pigmentation (84). (vi) Alpha and beta hydroxyl acids and derivatives. Alpha and beta hydroxyl acids have been the most important class of compounds that are most widely used in cosmetic prepara- tions. These act as superfi cial chemical peels that target the stratum corneum to improve skin color and tone. They are comparatively pure and inexpensive, and they may be used in higher amounts without many side effects (85). They are generally used in conjunction with other skin-lightening agents to improve performance. Also referred to as fruit acids, they improve skin texture by promoting desquamation or the shedding of the outer layers of the stratum corneum. Alpha hydroxyl acids (AHA) have also been noted to increase the enzymatic activity leading to epidermolysis. They are also employed in microderm- abrasion techniques. In addition, they act as moisturizers and promote the synthesis of elastin fi bers, leading to improved skin tone. However, care should be taken to neutralize the skin after AHA treatment, as it might cause burning and erythema. The most com- monly used AHAs are glycolic, lactic, citric, malic, pyurvic, and salicylic acids and their derivatives. THE EFFICACY OF SKIN-LIGHTENING FORMULATIONS Formulations for skin lightening have been majorly based on o/w emulsions that have a higher aesthetic appeal. The fact that many of the ingredients get better dispersions is also an added feature for the choice of such emulsions. Recently gel-based formulations are being considered for suitability in certain skin types. Effi cacy studies for skin-lightening formulations are carried out through clinical trails. Some of the techniques used in- volve the use of the mexameter, chromameter, spectrophotometer, and VISIA, along with