The sialidase inhibitor, DANA, reducesPorphyromonas gingivalispathogenicity and exerts anti-inflammatory effects: An in vitro and in vivo experiment

Background Sialidase has an important role in the pathogenesis of periodontitis andPorphyromonas gingivalisis a sialidase-producing organism implicated in periodontitis development. The aim of this study was to evaluate the anti-virulence and anti-inflammatory properties of the sialidase inhibitor, 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), in vitro and in vivo. Methods The effects of DANA onP. gingivalissialidase and cell viability were determined, and the effects of DANA onP. gingivalisvirulence were evaluated by assessment of growth curves, cell morphology, biofilm formation, fimbriae gene expression, and gingipains and lipopolysaccharide (LPS) activity. Anti-inflammatory effects of DANA on LPS-induced macrophages were assessed by measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1 beta), inducible nitric oxide synthase (iNOS) secretions. The effect of DANA onP. gingivalis-induced periodontitis in rats was analyzed by radiography, stereoscopic microscopy, histopathology, and immunohistochemistry. Results Sialidase inhibition rate of 1mM DANA was 72.01%. Compared with untreated controls, treatment with DANA inhibitedP. gingivalisgrowth and biofilm formation, and significantly decreased expression of thefimA,fimR, andfimSgenes, as well as gingipains activity. DANA did not influence macrophage viability, but significantly inhibited TNF-alpha, IL-1 beta, and iNOS production in LPS-stimulated macrophages. In the periodontitis rat model, DANA prevented alveolar bone absorption and inhibited TNF-alpha and IL-1 beta production. Conclusion DANA can reduce the growth, the biofilm formation and the virulence ofP. gingivalisand exhibits anti-inflammatory effects, as well as effects against rat periodontitis, suggesting that DANA should be considered for development as a new adjunctive treatment for periodontitis.