title: Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling.
abstract: OBJECTIVE
  To investigate the therapeutic effects of resveratrol (RSV) on periodontitis in diabetic mice and to explore the underlying mechanisms in vitro.
  
  
  METHODS
  Experimental periodontitis was induced in db/db mice by ligature application of porphyromonas gingivalis. The mice were treated with RSV (20 mg/kg, p.o.) daily for 4 weeks. Alveolar bone loss, proinflammatory cytokines and TLR4 expression in the gingival tissue were measured. Cultured gingival epithelial cells (GECs) were used for in vitro studies. The transcriptional activity of TLR4 downstream signaling was analyzed using Western blotting.
  
  
  RESULTS
  RSV administration significantly decreased the blood glucose levels, and ameliorated alveolar bone loss in db/db mice with experimental periodontitis. RSV administration also suppressed the high levels of IL-1β, IL-6, IL-8, TNF-α, and TLR4 in gingival tissue of the mice. In the GECs incubated in high glucose medium, TLR4 expression was substantially upregulated, which was partly blocked in the presence of RSV. Lipopolysaccharides markedly increased the expression and secretion of IL-1β, IL-6, IL-8, and TNF-α in the GECs cultured in high glucose medium, which was also partly blocked in the presence of RSV. Furthermore, RSV significantly suppressed the phosphorylation of TLR4 downstream factors NF-κB p65, p38MAPK, and STAT3.
  
  
  CONCLUSIONS
  RSV exerts protective effects against experimental periodontitis in db/db mice via negative regulation of TLR4 signaling.
authors.affiliation: Department of Periodontology, Shanghai Stomatological Disease Center, Shanghai 200001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: De-sheng
authors.initials: DS
authors.lastname: Fan
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai 200072, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, Shanghai Stomatological Disease Center, Shanghai 200001, China.
authors.forename: Xin-ming
authors.initials: XM
authors.lastname: Cao
authors.affiliation: Department of Periodontology, Shanghai Stomatological Disease Center, Shanghai 200001, China.
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Wang
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D013267:Stilbenes; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077185:Resveratrol