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-7α,11-diol (4), exhibited inhibitory effects with 27.4-34.1 and 39.0-56.9% reduction of melanin content at 50 and 100 μM, respectively, with no or very low toxicity to the cells (80.9-103.9% of cell viability at 100 μM). 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.
College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Tokyo 101-8308, Japan.
Takashi
T
Kikuchi
Kensuke
K
Watanabe
Yuichi
Y
Tochigi
Ayako
A
Yamamoto
Makoto
M
Fukatsu
Yoichiro
Y
Ezaki
Reiko
R
Tanaka
Toshihiro
T
Akihisa
D000818:Animals; D029403:Burseraceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012116:Resins, Plant / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000378:metabolism
D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D012116:Resins, Plant; D012717:Sesquiterpenes; D000521:alpha-MSH; D014442:Monophenol Monooxygenase