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The sialidase inhibitor, DANA, reduces Porphyromonas gingivalis pathogenicity and exerts anti‐inflammatory effects: An in vitro and in vivo experiment
Author(s) -
Yu Shiwen,
Fan Xiaomiao,
Zheng Shaowen,
Lin Li,
Liu Jingbo,
Pan Yaping,
Li Chen
Publication year - 2021
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1002/jper.19-0688
Subject(s) - porphyromonas gingivalis , microbiology and biotechnology , sialidase , in vivo , periodontitis , tumor necrosis factor alpha , lipopolysaccharide , biology , chemistry , immunology , medicine , neuraminidase , virus
Background Sialidase has an important role in the pathogenesis of periodontitis and Porphyromonas gingivalis is 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 on P. gingivalis sialidase and cell viability were determined, and the effects of DANA on P. gingivalis virulence 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‐α), interleukin (IL‐1β), inducible nitric oxide synthase (iNOS) secretions. The effect of DANA on P. 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 inhibited P. gingivalis growth and biofilm formation, and significantly decreased expression of the fimA , fimR , and fimS genes, as well as gingipains activity. DANA did not influence macrophage viability, but significantly inhibited TNF‐α, IL‐1β, and iNOS production in LPS‐stimulated macrophages. In the periodontitis rat model, DANA prevented alveolar bone absorption and inhibited TNF‐α and IL‐1β production. Conclusion DANA can reduce the growth, the biofilm formation and the virulence of P. gingivalis and 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.