Objectives: Periodontitis is a chronic inflammatory disease of bacterial etiology, affecting tooth-supporting tissues. The host inflammatory response to periodontal pathogens, notably the high and continuous production of cytokines, is considered a major factor causing the local tissue destruction observed in periodontitis. The Japanese apricot, known as Ume in Japanese, has been a traditional Japanese medicine for centuries, and is a familiar and commonly consumed food. The health benefits of Ume are now being widely recognized and have been strengthened by recent studies showing that MK615, an extract of compounds from Ume, has strong anticancer and anti-inflammatory effects. However, the potential role of MK615 in the periodontal field remains unknown. The aim of the present study was to investigate the effect of MK615 on tumor necrosis factor-alpha (TNF-α) production in murine macrophage-like RAW264.7 cells (RAW264.7 cells) stimulated by Porphyromonas gingivalis (P.gingivalis) lipopolysaccharide (LPS), a major etiological agent in localized chronic periodontitis.
Methods: The effect of MK615 was characterized using RAW264.7 cells stimulated with the LPS of P. gingivalis in the presence or absence of MK615. LPS-induced TNF-α production by RAW264.7 cells treated with MK615 were evaluated using an enzyme-linked immunosorbent assay. Changes in the phosphorylation states of macrophage kinases induced by P. gingivalis LPS and/or MK615 were characterized by westernblotting. The nuclear translocation of NF-κB was determined by immunofluorescence.
Results: Our results clearly indicated that MK615 is a potent inhibitor of TNF-α response induced by P. gingivalis LPS in RAW264.7 cells. MK615 markedly inhibited the phosphorylation of ERK1/2, p38MAPK and JNK, which is associated with pro-inflammatory mediator release pathways. Moreover, MK615 completely blocked LPS-triggered NF-κB activation.
Conclusion: The results from the present study suggest that MK615 holds promise as a therapeutic agent for treating inflammatory diseases such as periodontitis.