Achieving safe and effective skin whitening

 Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Skin whitening agents often inhibit the activity of tyrosinase, for example, by competitive or non-competitive inhibition of its catalytic activity, by inhibiting its maturation, or by accelerating its degradation. The cosmetic industry is looking for novel, effective, possibly ‘natural’ ingredients of low or absent side effects. With hydroquinone, the previous benchmark in this field, fast and effective results to whiten skin were obtained. The drawback of the fast effect was the high cytotoxicity of hydroquinone and its huge irritation potential. New active ingredients with a much improved toxicology profile have been developed instead. They often provide the whitening effect in a reversible way, demonstrating that the biology of melanin production will only be suppressed during treatment but not destroyed. These new kinds of natural whitening ingredients however force us to become more patient. They do work well if they get the time the biochemistry of the skin needs and surprisingly they can even provide skin protection.

Up to 10% of skin cells in the basal layer of the epidermis produce melanin. Upon exposure of the skin to UV irradiation, melanogenesis is initiated with the first step of tyrosine oxidation through tyrosinase. Tyrosinase is a multifunctional, glycosylated, copper-containing oxidase. It is synthesised by melanosomal ribosomes found on the rough endoplasmic reticulum (ER). After synthesis, tyrosinase is glycosylated. It is subsequently delivered to melanosomes via coated vesicles in an inactive form. The biosynthetic pathway for melanin formation in various life forms has largely been elucidated by Raper (1928), Mason (1948) and Lerner et al (1949). Melanins also play a crucial role in the absorption of free radicals generated within the cytoplasm and in shielding the host from various types of ionising radiations, including UV light. Melanins can be of two basic types: eumelanins, which are brown or black, and pheomelanins, which are red or yellow. The metabolic pathways are illustrated in Figure 1. In mammals, mixtures of both types are typically found.1 Multiple potential approaches exist that could control pigmentation via the regulation of tyrosinase activity. The transcription of its messenger RNA, its maturation via glycosylation, its trafficking to melanosomes, as well as modulation of its catalytic activity and/or stability could be regulated. Tyrosinase is produced only by melanocytic cells and following its synthesis and subsequent processing in the endoplasmic reticulum (ER) and Golgi apparatus, it is trafficked to specialised organelles, termed melanosomes, wherein the pigment is synthesised and deposited.2

Well-known tyrosinase inhibitors