Department of Dysphagia Rehabilitation, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Department of Microbiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan.
J Nat Med. 2019 Jan;73(1):114-123. doi: 10.1007/s11418-018-1250-6. Epub 2018 Sep 14.
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.
牙周病是全球影响超过一半成年人的主要公共卫生问题。牙周病病原菌牙龈卟啉单胞菌产生的脂多糖（LPS）诱导炎症细胞因子的表达，促进炎症性骨破坏。越来越多的证据表明，牙周病与几种系统性疾病的发生和发展有关，如吸入性肺炎和糖尿病。虽然通过刷牙去除牙周病原菌来治疗牙周病是一种标准做法，但它有其局限性，并非在所有情况下都有效。因此，需要一种新的方法来替代或补充刷牙，以治疗牙周病。在这项研究中，我们研究了羽衣甘蓝提取物及其药理有效化合物芹菜素（一种倍半萜内酯）对 LPS 刺激的人牙龈成纤维细胞（HGF）的抗炎作用，以及对 RAW264.7 细胞中核因子-κB 受体激活剂配体（RANKL）诱导的破骨细胞生成的潜在抗生成作用。我们发现，芹菜素以剂量依赖的方式抑制 LPS 刺激的 HGF 中 IL-8 和 IL-6 mRNA 和蛋白的合成。P. gingivalis LPS 诱导的 IκBα降解和 NF-κB p65磷酸化也被芹菜素抑制，LPS 刺激的 NF-κB 转激活也被抑制。因此，芹菜素抑制 P. gingivalis LPS 诱导的 IL-8 和 IL-6 表达可能是由于抑制了 NF-κB 途径。此外，我们表明，芹菜素显著减少了 RANKL 诱导的破骨细胞分化。这些结果表明，芹菜素可能有助于预防牙周病，并可能为开发更有效的牙周病预防方法提供价值。
