Arbutin was first discovered in Arctostapylos uva-ursi (L.) Spreng and then in the leaves of Vaccinicum vitis-idaca L., Pyrus pyrifolia (Burm. f.) Kakai. and Saxifraga stolonifera (L.) Meerb. It is a naturally occurring HQ beta-D-gluconopyranoside, which causes depigmentation at non-cytotoxic concentrations. In both normal human melanocytes and melanoma, arbutin induces a decrease of tyrosinase activity without affecting messenger RNA (mRNA) expression, inhibits the 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymerase activity (pmel 17/silver protein) (27), and exerts an inhibitory effect on melanosome maturation. It was found to inhibit the oxidation of l-tyrosine catalyzed by mushroom tyrosinase (28). The kinetics and mechanism for inhibition of tyrosinase confirms the reversibility of arbutin as a competitive inhibitor of this enzyme (29). Arbutin was much less cytotoxic than HQ to cultured human melanocytes.
A clinical trial performed with Japanese women with melasma found a 3% arbutin – containing skin lotion, milky lotion and cream, applied twice daily for three months, to be effective in reducing melasma intensity and lesion size (good-to-excellent clinical response in 71.4% of patients) (30). Higher concentrations are more efficacious than lower concentrations, but they may also result in a paradoxical hyperpigmentation.