Inhibitory Effects of Sudachitin on the Production of Inflammation-related Molecules in Human Gingival Fibroblasts Cultured under High Glucose Conditions

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  • Yasufumi NISHIKAWA
    Department of Oral Implant Center, Tokushima University Hospital
  • Koji NARUISHI
    Department of Periodontics, Tokushima University Hospital
  • Jun-ichi KIDO
    Department of Periodontology and Endodontology, Tokushima University Graduate School of Biomedical Sciences
  • Hiromichi YUMOTO
    Department of Periodontology and Endodontology, Tokushima University Graduate School of Biomedical Sciences

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Other Title
  • 高グルコース条件下における歯肉線維芽細胞のカルプロテクチン誘導性炎症関連因子の産生におけるスダチチンの抑制効果

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Abstract

<p> Purpose: Diabetic patients are susceptible to severe periodontitis. Sudachitin, which is a polymethoxyflavone derived from the peel of Citrus sudachi, possesses antioxidant properties. The purpose of this study was to explore the biological activities of Sudachitin on severe periodontitis in diabetic patients by targeting human gingival fibroblasts (HGFs) cultured under high glucose (HG) conditions.</p><p> Methods: HGF cell line CRL-2014 (ATCC) was maintained in DMEM containing 5.5 mmol/l glucose (normal glucose condition, NG) or 25 mmol/l glucose (HG), and cells were stimulated with calprotectin. To investigate the productivity of MCP-1, IL-6, MMP-1 and TIMP-1 after calprotectin stimulation, cell supernatants were collected for enzyme-linked immunosorbent assay. Next, total cell lysates were collected for western-blotting in order to investigate the NF-κB signaling after calprotectin stimulation. To examine the effects of Sudachitin on the production of inflammation-related molecules or NF-κB signaling, Sudachitin was added 60 min prior to the calprotectin stimulation.</p><p> Results: Calprotectin increased MCP-1, IL-6 and MMP-1 production significantly in HGFs. HG enhanced significantly calprotectin-induced production of MCP-1 and MMP-1, but not IL-6. Sudachitin suppressed calprotectin-induced MCP-1 and MMP-1 production in HGFs cultured with both NG and HG significantly. Sudachitin also inhibited dramatically the calprotectin-induced IκBα and p65 phosphorylation.</p><p> Conclusion: HG enhances calprotectin-induced production of MCP-1 and MMP-1 in HGFs. Sudachitin suppresses MCP-1 and MMP-1 production in HGFs via the NF-κB pathway. Sudachitin might be a useful polyphenol for severe periodontitis in diabetic patients.</p>

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