Survey and mechanism of skin depigmenting and lightening agents

Abstract The type and amount of melanin synthesized by the melanocyte, and its distribution pattern in the surrounding keratinocytes, determines the actual color of the skin. Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Tyrosinase catalyses three different reactions in the biosynthetic pathway of melanin in melanocytes: the hydroxylation of tyrosine to l ‐DOPA and the oxidation of l ‐DOPA to dopaquinone; furthermore, in humans, dopaquinone is converted by a series of complex reactions to melanin. Among the skin‐lightening and depigmenting agents, magnesium‐ l ‐ascorbyl‐2‐phosphate (MAP), hydroxyanisole, N ‐acetyl‐4‐S‐cysteaminylphenol, arbutin (hydroquinone‐beta‐ d ‐glucopyranoside) and hydroquinone (HQ) are the most widely prescribed worldwide. However, with reports of potential mutagenicity and epidemics of ochronosis, there has been an increasing impetus to find alternative herbal and pharmaceutical depigmenting agents. A review of the literature reveals that numerous other depigmenting or skin‐lightening agents are either in use or in investigational stages. Some of these, such as kojic, glycolic and azelaic acids, are well known to most dermatologists. Others have been discovered and reported in the literature more recently. Several depigmentation and lightening agents are discussed, including their historical background, biochemical characteristics, type of inhibition and activators from various sources. In addition, the clinical importance of mushroom tyrosinase as a recent prospect is discussed in this paper. Copyright © 2006 John Wiley & Sons, Ltd.