Archives of Pharmacal Research

, Volume 37, Issue 5, pp 567–574 | Cite as

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

  • Soo-Jin Choo
  • In-Ja Ryoo
  • Kwan Chul Kim
  • Minkyun Na
  • Jae-Hyuk Jang
  • Jong Seog Ahn
  • Ick-Dong YooEmail author
Research Article


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.


Inula britannica Sesquiterpenes Melanogenesis Tyrosinase ERK Akt 



This work was supported by the INNOPOLIS Foundation of Korea grant funded by the Ministry of Science, ICT & Future Planning and Global R & D Center Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (MEST).


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Copyright information

© The Pharmaceutical Society of Korea 2014

Authors and Affiliations

  • Soo-Jin Choo
    • 1
    • 2
  • In-Ja Ryoo
    • 1
  • Kwan Chul Kim
    • 3
  • Minkyun Na
    • 2
  • Jae-Hyuk Jang
    • 1
  • Jong Seog Ahn
    • 1
  • Ick-Dong Yoo
    • 1
    Email author
  1. 1.Chemical Biology Research CenterKorea Research Institute of Bioscience and BiotechnologyCheongwonRepublic of Korea
  2. 2.College of PharmacyChungnam National UniversityYuseong-guRepublic of Korea
  3. 3.Innoskin Co., Ltd., 209 BVCKorea Research Institute of Bioscience and BiotechnologyYuseong-guRepublic of Korea

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