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

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An Erratum to this article was published on 25 March 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.

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Acknowledgments

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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Authors and Affiliations

  1. Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongwon, Chungbuk, 363-883, Republic of Korea

    Soo-Jin Choo, In-Ja Ryoo, Jae-Hyuk Jang, Jong Seog Ahn & Ick-Dong Yoo

  2. College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Republic of Korea

    Soo-Jin Choo & Minkyun Na

  3. Innoskin Co., Ltd., 209 BVC, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, Republic of Korea

    Kwan Chul Kim

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  1. Soo-Jin Choo
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Choo, SJ., Ryoo, IJ., Kim, K.C. et al. Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells. Arch. Pharm. Res. 37, 567–574 (2014). https://doi.org/10.1007/s12272-013-0302-4

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