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j. Cosmet. sci., 54, 133-142 (March/April 2003) Inhibitory effects of Iamulus mori extracts on melanogenesis KANG TAE LEE, KWANG SIK LEE, JI HEAN JEONG, BYOUNG KEE JO, MOON YOUNG HEO, and HYUN PYO KIM, Corearia Cosmetics Co., 204-1 JeongchonRi, Senggeoeup, Cheonansi, 330-830 (K.T.L., K.S.L., j.H.j., B.K.J.), and College of Pharmacy, Kangwon National University, 200-701 (M. Y.H., H.P.K.), Korea Accepted for publication December 18, 2002. Synopsis To develop an active agent for skin whitening, the inhibitory effects of 285 plant extracts on tyrosinase activity were examined, and one plant extract having tyrosinase inhibition activity was chosen. Ramulus mori (young twigs of Moru• alba L.) extracts showed inhibition activity in tyrosinase and melanin synthesis in B-16 melanoma cells. To clarify the mechanism of its inhibition on melanogenesis, the effect of R. mori extracts on tyrosinase activity, synthesis, and gene expression was evaluated. R. mori extracts showed tyrosinase inhibition activity by competitive method, and there was no suppression of tyrosinase synthesis and gene expression. Further, to evaluate the inhibitory activity of R. mori in vivo, its effect on melanin production in UV-induced brown guinea pigs was examined, where a decrease of melanin production in the guinea pig model was observed. Also, R. mori extracts showed no toxicity in animal tests such as the acute toxicity test, the skin irritation test, the eye irritation test, the skin sensitization test, and the acute oral toxicity test, and no toxicity in the human skin irritation test. A single compound from R. mori extracts was purified using various column chromatography and recrys- tallization, and its chemical structure was identifed using mass chromatography, IR spectroscopy, and NMR analysis. The chemical structure was that of 2,3',4,5'-tetrahydroxystilbene(2-oxyresveratrol) and showed inhibition activity on tyrosinase (IC5o = 0.23 pg/ml). Also, R. mori extracts inhibited tyrosinase activity in a competitive manner (Ki = 1.5 x 10 6 M) when L-tyrosine was used as a substrate. INTRODUCTION It has been observed that the increase of melanin synthesis or uneven distribution can cause local pigmentation in the skin. Pigmentary disorders are caused by various factors, including UV radiation, inflammation, estrogens, and genetic disorders. Recently, the harmfulness of ultraviolet rays has increased due to the destruction of the ozone layer. Excessive exposure to UV radiation may cause post-inflammatory pigmentation (1). In East Asia, most women want to avoid uneven skin pigmentation. To satisfy this desire many cosmetic companies have been developing melanogenesis inhibitors and discov- 133