Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells

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Title
Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells
Author(s)
Soo Jin Choo; In-Ja Ryoo; K C Kim; M Na; Jae-Hyuk Jang; Jong Seog Ahn; Ick-Dong Yoo
Bibliographic Citation
Archives of Pharmacal Research, vol. 37, no. 5, pp. 567-574
Publication Year
2014
Abstract
During the course of screens to identify anti-melanogenic agents from natural resources, we found that the methanol extract of the dried flower of Inula britannica L. inhibited melanin synthesis in cultured melanoma cells stimulated with 3-isobutyl-1-methylxanthine (IBMX). A bioassay-guided isolation of the chloroform fraction of the I. britannica using an in vitro melanogenesis inhibition assay led to the isolation of sesquiterpenes, 1-O- acetylbritannilactone (1), britannilactone (2) and neobritannilactone B (3). Compounds 1 and 2 significantly reduced melanin production in a dose-dependent manner with IC50 values of 13.3 and 15.5 μM, respectively, whereas compound 3 was found to be cytotoxic. Compound 1 also inhibited the tyrosinase activity only in cell based-systems. Western blot analysis indicated that compound 1 inhibited melanogenesis by activating extracellular signal-regulated kinase (ERK) and Akt signaling and also inhibiting cAMP related binding protein, which regulates its downstream pathway, including tyrosinase, tyrosinase related protein-1 and TRP-2. These results demonstrated that compound 1, a major sesquiterpene from the flowers of I. britannica, exhibited anti-melanogenic activity by suppression of tyrosinase expression via ERK and Akt signaling. Taken together, our results suggest that these compounds may act as potent natural skin-lightening agents.
Keyword
AktERKInula britannicaMelanogenesisSesquiterpenesTyrosinase
ISSN
0253-6269
Publisher
Pharmaceutical Soc Korea
DOI
http://dx.doi.org/10.1007/s12272-013-0302-4
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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