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    1. Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on melanin synthesis.
    Yutaka Tokiwa, Masaru Kitagawa, Takao Raku, Shusaku Yanagitani, Kenji Yoshino. National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. Available online 16 March 2007.

    "Transesterification of arbutin and undecylenic acid vinyl ester was catalyzed by alkaline protease, Bioprase, in dimethylformamide to get arbutin derivative having undecylenic acid at 6-position of glucose moiety, 6-O-undecylenoyl p-hydroxyphenyl Beta-d-glucopyranoside. The reaction rate increased with increase of arbutin concentration, and when its concentration was 0.9 M, the conversion rate was more than 90% under addition of 2 M undecylenic acid vinyl ester. The obtained arbutin ester significantly suppressed melanin production in murine B16 melanoma cells."

    2. High-performance liquid chromatographic determination of arbutin in skin-whitening creams and medicinal plant extracts.
    WISANU THONGCHAI, BOONSOM LIAWRUANGRATH, and SAISUNEE LIAWRUANGRATH, Department of Pharmaceutical Sciences, Faculty of Pharmacy (W. T., B.L.), and Department of Chemistry, Faculty of Science (S.L.), Chiang University, Chiang Mai, 50200, Thailand. Accepted for publication November 1, 2006.

    "Arbutin is found in the bark and leaves of various plants, usually occurring together with methylarbutin. Naturally occurring arbutin was first characterized by Kawalier (3), who obtained it from bearberry leaves. It is also found in the leaves of blueberry, cranberry, and pear. Synthetic arbutin was first reported by Mannich (4), and later by others. Commercial arbutin is almost always synthetic in origin. Because of its antibacterial properties, arbutin is a constituent of the traditional medicine, and it is widely used in a variety of formulations (5). The ability of arbutin to inhibit human melanin synthesis has given rise to its wide use in many cosmetic formulations (6). Arbutin protects the skin against damage caused by free radicals. It is a skin-whitening agent that is very popular in Japan and Asian countries for skin depigmentation. Arbutin inhibits the formation of melanin pigment by inhibiting tyrosinase activity (7)."

    3. AEfficiency of ellagic acid and arbutin in melasma: A randomized, prospective, open-label study.
    Ilgen ERTAM, Basak MUTLU, Idil UNAL, Sibel ALPER, Bijen KIVCAK, Ozgen OZER. Article first published online: 20 SEP 2008.

    "The aim of this study was to compare the effectiveness of gel formulations containing arbutin, synthetic ellagic acid and plant extracts that contain ellagic acid, on patients with melasma. Thirty patients who applied to Ege University Medical Faculty, Department of Dermatology, were included in the study. A signed consent was obtained from each patient prior to study. Patients whose type of melasma was determined via Wood's lamp were randomized to groups of arbutin, synthetic ellagic acid and plant extract containing natural ellagic acid. The pigment density of patients was evaluated via Mexameter before and after the treatment. The approval of the Institutional Ethics Committee of Ege University was obtained before the study. Wilcoxon and Kruskal–Wallis tests were used in the statistical analysis. Nine of 10 patients, for whom synthetic ellagic acid was started, completed the study. A decrease in the level of melanin was determined in eight of these nine patients (P = 0.038). A significant decrease in the level of melanin was also determined in all 10 patients who used plant extract containing ellagic acid (P = 0.05). A significant response was obtained from all of 10 patients who used arbutin. The difference between pre- and post-treatment levels of melanin was statistically significant (P = 0.05). Formulations prepared with plant extracts containing ellagic acid was found effective on melasma, similar to the formulations containing synthetic ellagic acid and arbutin. This material that is not yet being used widespread commercially on melasma could be an effective alternative for treatment of melasma."