SKIN-LIGHTENING COSMETIC INGREDIENTS 47 (MBEH) and monomethyl ether of hydoquinone (MMEH) also demonstrate tyrosinase inhibitory properties (37–39). Further, they also cause melanocyte loss through genera- tion of free radicals. However, the use of these compounds for depigmentation is limited by their adverse effects, similar to those of hydroquinone. (b) ARBUTIN. Arbutin is a naturally occurring β,D-glycopyranoside derivative of hydro- quinone. Although it shows tyrosinase inhibition, it is not found to affect RNA synthe- sis as does hydroquinone. The α-derivative shows a stronger inhibitory effect on tyrosinase and melanosome maturation (40,41). It is also present in many of the botanical extracts. Arbutin is highly pH-sensitive and can hydrolyze to hydroquinone at both acidic and alkaline pH. Hence, care should be taken during use in commercial skin-lightening products. (c) KOJIC ACID. Kojic acid is a powerful tyrosinase inhibitor. It functions by the chelation of copper at the active site of the enzyme tyrosinase (42). Further, it acts as an antioxidant and a free radical scavenger. Although powerful, the use of kojic acid is under scrutiny by dermatologists because of its adverse side effects such as allergic dermatitis (43). It is found to be unstable in formulations and may also cause discoloration. Some stable derivatives, such as kojic acid dipalmitate, are being used to enhance effectiveness by enhanced skin penetration. Thus there exists a demand for safe and effective alternative botanicals as preferred skin-lightening ingredients. Figure 3. Structures of some skin-lightening agents.

JOURNAL OF COSMETIC SCIENCE 48 (ii) Botanical extracts. Extracts mostly contain a combination of two or more classes of com- pounds that work synergistically to achieve skin lightening. Botanicals connote nature and are hence more acceptable to people. Further, a large number of yet undiscovered plants are available to provide for exotic products and claims for cosmetics. However, it should also be observed that natural extracts may be highly unstable and may not be compatible within formulations. A large number of ingredients (Table I) have been studied for tyrosinase inhi- bition and have been processed to make them viable for use in cosmetic products. These are available commercially through suppliers for use as skin-lightening agents. (iii) Antioxidants as skin-lightening agents. Antioxidants serve to reduce oxidation of tyrosine to DOPA quinone and therefore are shown to have skin-lightening activity (64). In addition, they act in the melanogenesis pathway, reducing the synthesis of melanin. Exposure to UV radiation results in the generation of free radicals. It has been identifi ed that ROS (reactive oxygen species) are able to oxidize tyrosinase and DOPA to melanin, and this is one of the major causes for tanning (65). Although antioxidants are present in tissues, they may not be able to reduce the radicals, depending on the extent of UV expo- sure. Infl ammation is a source of free radicals. Hence the quenching of free radicals would also help in reducing the synthesis of melanin, thereby contributing to skin depigmenta- tion effects (66). The use of phytic acid, glutathione (Figure 4), and ubiquinone as popu- lar skin-lightening agents is due to their strong antioxidant nature (67–68). Melanin synthesis in melanocytes is accompanied by the generation of hydrogen peroxide that can lead to the formation of ROS that further increase the proliferation of melanocytes. Table I Botanicals That are Mostly Used in Skin-Lightening Cosmetics S. No. Extract Type Reference 1 Morus alba extract 2-Oxyresveratrol 44 2 Aloe barbadensis leaf extract Aloesin 45 3 Crocus sativus extract Kaempferol 46 4 Uva ursi Arbutin 47 5 Licorice extract Glabridin 48 6 Camelia sinesis extract ECG 49 7 Phylanthus embelica extract Vitamin C 50 8 Citrus limonum extract Hisperidin 51 9 Punica granatum extract Ellagitannins 52 10 Vitis vinifera (grape) fruit extract Procyanidins 53 11 Anise extract Anisic acid 54 12 Cumin seed extract Cumic acid 55 13 Cinnamonum cassia extract Trans-cinnamaldehyde 56 14 Artocarpus lakoocha heartwood extract 2-Oxyresveratrol 57 15 Purus comunis (pear) extract Arbutin 58 16 Geranium extract Ellagic acid 59 17 Ramulus mori extract 2-Oxyresveratrol 60 18 Ginseng extract p-Coumaric acid 61 19 Malpighia punicifolia (Acerola) fruit extract Polyphenols 62 20 Mushroom (Agaricus blazei Muril) extract Tri-terpenoids 63