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Cynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells

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Abstract

Periodontal diseases are a major public health problem affecting over half of the adult population worldwide. Lipopolysaccharide (LPS) produced by the periodontopathic bacterium Porphyromonas gingivalis induces the expression of inflammatory cytokines that promote inflammatory bone destruction. Mounting evidence supports that periodontal diseases are involved in the onset and progression of several systemic diseases, such as aspiration pneumonia and diabetes. Although treatment of periodontal diseases by removing the periodontopathic bacteria by brushing is a standard practice, it has limitations and is not effective in all cases. Therefore, a new method to replace or complement brushing is needed for the treatment of periodontal diseases. In this study, we investigated the anti-inflammatory effects of an extract from Cynara scolymus L. and its pharmacologically effective compound cynaropicrin, a sesquiterpene lactone, on human gingival fibroblasts (HGFs) stimulated by LPS and the potential anti-osteoclastogenic effects on RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL). We found that cynaropicrin inhibited IL-8 and IL-6 mRNA and protein synthesis in LPS-stimulated HGFs in a dose-dependent manner. P. gingivalis LPS-induced degradation of IκBα and phosphorylation of NF-κB p65 were also suppressed by cynaropicrin, as was LPS-stimulated NF-κB transactivation. Thus, cynaropicrin’s inhibition of P. gingivalis LPS-induced IL-8 and IL-6 expression may be due to the inhibition of the NF-κB pathway. Furthermore, we showed that cynaropicrin dramatically reduced RANKL-induced osteoclast differentiation. These results suggest that cynaropicrin may be useful for preventing periodontal diseases and could prove valuable in the development of more effective preventative approaches for periodontal diseases.

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Acknowledgements

This work was supported by JSPS KAKENHI, the Dental Research Center, Nihon University School of Dentistry, and the Nihon University Multidisciplinary Research Grant for 2017.

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Authors and Affiliations

  1. Department of Dysphagia Rehabilitation, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan

    Mayumi Hayata & Kouichiro Ueda

  2. Department of Microbiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan

    Mayumi Hayata, Norihisa Watanabe, Noriaki Kamio, Muneaki Tamura, Keiko Nodomi & Kenichi Imai

  3. Department of Periodontology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan

    Norihisa Watanabe & Shuichi Sato

  4. Department of Research and Development, Ichimaru Pharcos Co. Ltd, Gifu, Japan

    Kiyotaka Tanaka & Arunasiri Iddamalgoda

  5. Department of Biochemistry, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan

    Hiromasa Tsuda

  6. Department of Periodontology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan

    Yorimasa Ogata

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  1. Mayumi Hayata
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  2. Norihisa Watanabe
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Correspondence to Kenichi Imai.

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Hayata, M., Watanabe, N., Kamio, N. et al. Cynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells. J Nat Med 73, 114–123 (2019). https://doi.org/10.1007/s11418-018-1250-6

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  • DOI: https://doi.org/10.1007/s11418-018-1250-6

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