D

Maeda and Fukuda, 1996 Maeda K.

Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture.

Chakraborty et al., 1998 Chakraborty A.K.

Funasaka Y.

Komoto M.

Ichihashi M. Effect of arbutin on melanogenic proteins in human melanocytes.

Sugimoto et al., 2004 Sugimoto K.

Nishimura T.

Nomura K.

Sugimoto K.

Kuriki T. Inhibitory effects of alpha-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model.

Boissy et al., 2005 Boissy R.E.

Visscher M.

DeLong M.A. DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency.

Arbutin, a naturally occurring β--glucopyranoside derivative of hydroquinone, exists in the dried leaves of certain plant species, such as bearberry. The mode of action appears to be by inhibition of melanosomal tyrosinase and DHICA (5,6-dihydroxyindole-2-carboxylic acid) polymerase activities at noncytotoxic concentrations rather than by suppression of the synthesis and expression of this enzyme (). It is thought that the activity of arbutin is driven by the structural homologies that it shares with the substrate tyrosine, which leads to the competitive inhibition of the catalytic function of tyrosinase. Studies have shown that α-arbutin (4-hydroxyphenyl α-glucopyranoside) demonstrates an even stronger inhibitory effect on human tyrosinase activity than arbutin itself. This effect was achieved without affecting mRNA expression of enzyme in cultured human melanoma cells and a three-dimensional human skin model (). Deoxyarbutin (dA, 4-[tetrahydrofuran-2-yl-oxy]-phenol) has also demonstrated effective inhibition of mushroom tyrosinase in vitro. In a human clinical trial, topical treatment with dA for 12 weeks resulted in a significant or a slight reduction in overall skin lightness and improvement of solar lentigines in a population of light-skinned or dark-skinned individuals, respectively (). α-Arbutin has widely replaced arbutin as the chosen skin-lightening agent in topical skin preparations because it is more effective and stable in producing the desired effects on human skin.