Melanogenesis Inhibitory Activity of Sesquiterpenes from Canarium ovatum Resin in Mouse B16 Melanoma Cells

Four known sesquiterpene alcohols, i.e. , 1 – 4 , ten triterpene alcohols, i.e. , 5 – 14 , and four triterpene acids, i.e. , 15 – 18 , were isolated from the MeOH extract of Canarium ovatum resin (elemi resin). Upon evaluation of the previously described compounds 1 – 18 on the melanogenesis in B16 melanoma cells induced with α ‐melanocyte‐stimulating hormone ( α ‐MSH), three sesquiterpene alcohols, i.e. , cryptomeridiol ( 1 ), 4‐epicryptomeridiol ( 2 ), and cadin‐1(14)‐ene‐7 α ,11‐diol ( 4 ), exhibited inhibitory effects with 27.4–34.1 and 39.0–56.9% reduction of melanin content at 50 and 100 μ M , respectively, with no or very low toxicity to the cells (80.9–103.9% of cell viability at 100 μ M ). Western ‐blot analysis revealed that compounds 1 and 2 reduced the protein levels of MITF (=microphtalmia‐associated transcription factor), tyrosinase, and TRP‐2 (=tyrosine‐related protein 2), mostly in a concentration‐dependent manner, suggesting that these compounds exhibit melanogenesis inhibitory activity on α ‐MSH‐stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase and TRP‐2. Three sesquiterpene alcohols, i.e. , 1, 2 , and 4 , are, therefore, considered to be valuable as potential skin‐whitening agents.