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Induction of melanogenesis by 4′-O-methylated flavonoids in B16F10 melanoma cells

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Abstract

Agents to control melanogenesis are in demand for the development of cosmetics to improve pigmentation disorders of skin and hair. In this study, we examined and evaluated the effects of flavonoids on melanogenesis in the melanogenic cells model, murine B16F10 melanoma cells. In the course of this study, we found that incubation of the cells in a medium containing 10 μM of the 4′-O-methylated flavonoids, diosmetin (4′-O-methylluteolin), acacetin (4′-O-methylapigenin) or kaempferide (4′-O-methylkaempferol), increased the melanin contents of the cells 3- to 7-fold higher than the control cells. The concentration-dependence test revealed that 20 μM acacetin showed the highest effect, up to 33-fold higher than the vehicle. On the other hand, the corresponding 4′-OH-type flavonoids, luteolin, apigenin and kaempferol, had a significantly smaller effect. Furthermore, by evaluating the melanogenic proteins, we found that the cells treated with 4′-O-methylated flavonoids showed higher tyrosinase activity, as well as upregulation of tyrosinase expression, preceded by activation of cAMP response element binding protein (CREB) and extracellular signal-regulated kinases types 1 and 2 (ERK1/2). These results indicate that the 4′-O-methyl group of flavonoids plays an important role in the induction of melanogenesis by activating its major signal transduction pathway through the upregulation of phospho-CREB in murine B16F10 melanoma cells.

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Authors and Affiliations

  1. Nakano Seiyaku Co. Ltd, 6-20 Kitainoue-cho, Higashino, Yamashina-ku, Kyoto, 607-8141, Japan

    Ippei Horibe, Shuji Sugie & Katsuyoshi Obata

  2. Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho Suita, Osaka, 564-8680, Japan

    Yudai Satoh, Yuki Shiota, Ayako Kumagai, Nanao Horike, Shinichi Uesato, Hidehisa Kawahara & Yasuo Nagaoka

  3. Laboratory of Cell Signaling and Metabolic Disease, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan

    Ayako Kumagai, Nanao Horike & Hiroshi Takemori

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  1. Ippei Horibe
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  2. Yudai Satoh
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  3. Yuki Shiota
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  4. Ayako Kumagai
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Correspondence to Katsuyoshi Obata.

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Horibe, I., Satoh, Y., Shiota, Y. et al. Induction of melanogenesis by 4′-O-methylated flavonoids in B16F10 melanoma cells. J Nat Med 67, 705–710 (2013). https://doi.org/10.1007/s11418-012-0727-y

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  • DOI: https://doi.org/10.1007/s11418-012-0727-y

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