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J. Cosrnet. Sci. J 57, 11-21 CTanuary/February 2006) New cosmetic agents for skin whitening from Angelica dahurica Y. H. CHO, J. H. KIM, S. M. PARK, B. C. LEE, H. B. PYO, and H. D. PARK, R&D Center, Hanbul Cosmetic CorporationJ 72-7 Yongsung-ri, Samsung-myun, Umsung-kun, Chungbuk 369-834 (Y.H.C., ].H.K., S.M.P., B.C.L., H.B.P.), and Department of Biotechnology, College of Engineering, Daegu University, Gyeongsan-si, Gyeongbuk 712-714 (H.D.P.) Korea. Accepted for publication on August 9, 2005. Synopsis To develop a new whitening agent for cosmetics from natural products, Angelica dahurica was selected for its inhibitory effect on melanogenesis in Bl6 melanoma cells. From the mechanism study, it was clarified that the ethanolic extracts of this plant showed the suppression of tyrosinase synthesis but no inhibition of tyrosinase activity. In order to find the active constituents from this plant, the ethanol extracts were chromatographed repeatedly with silica gel. Two coumarin compounds were isolated from A. dahurica. Their structures were identified by physicochemical and spectral data such as UV, IR, NMR, and MS. It was shown that the active substance was isoimperatorin (10-[(3-methyl-2-butenyl)oxy}-7H-furo[3,2-g}[l} ben- zopyran-7-one) and imperatorin (9-[(3-methyl-2-butenyl)oxy }-7H-furo[3,2-g}[l} benzopyran-7-one). They significantly inhibited tyrosinase synthesis in B 16 melanoma cells. To elucidate the action mechanism of the active compounds of A. dahurica, we investigated the changes in the mRNA level of tyrosinase using the RT-PCR technique. As a result, the mRNA level of tyrosinase was markedly reduced by active compounds of A. dahurica. From these results, we suggest that these extracts might be useful as a new whitening agent in cosmetics, but the in vitro findings must be verified in in vivo skin-lightening studies. INTRODUCTION Melanin production is principally responsible for skin color and plays an important role in the prevention of sun-induced skin injury (1). However, abnormal hyperpigmentation such as freckles, chloasma, lentigines, and other forms of melanin hyperpigmentation could be a serious aesthetic problem (2). In mammalian melanocytes, melanins are synthesized within melanosomes that contain tyrosinase, which plays a key role in melanogenesis, as it catalyzes the rate-limiting reaction of the melanogenic process (3-5). Accordingly, melanin production is mainly controlled by the expression and activation of tyrosinase ( 6). Address all correspondence to Y. H. Cho. 11
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