RESUMO
Fisetin is an anti-inflammatory flavonoid; however, its anti-inflammatory mechanism is not yet understood. In this study, we evaluated the anti-inflammatory effect of fisetin and its association with mitogen-activated protein kinase (MAPK) and nuclear factor kappa-beta pathways in human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) obtained from Porphyromonas gingivalis. The cell signaling, cell viability, and cyclooxygenase-2 (COX-2) expression of HGFs treated with various concentrations (0, 1, 5, 10, and 15 µM) of fisetin were measured by cell viability assay (MTT), Western blotting, and reverse transcriptase polymerase chain reaction analysis on COX-2. We found that fisetin significantly reduced the synthesis and expression of prostaglandin E2 in HGFs treated with LPS. Activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK was suppressed consistently by fisetin in HGFs treated with LPS. The data indicate that fisetin inhibits MAPK activation and COX-2 expression without affecting cell viability. These findings may be valuable for understanding the mechanism of the effect of fisetin on periodontal disease.
Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Dinoprostona/metabolismo , Fibroblastos/efeitos dos fármacos , Flavonoides/química , Flavonóis , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Porphyromonas gingivalis/citologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Periodontitis is an inflammatory process of infectious origin that affects the gums and, in severe cases, destroys connective tissue, leading to loss of the dental organ. Gram-negative Porphyromonas gingivalis bacteria are recovered from patients with chronic periodontitis. The polysaccharide obtained from these bacteria induces the expression of interleukin (IL)-1 beta, tumor necrosis factor, and IL-6. Flavonoids are molecules that participate in the control of inflammatory processes. We studied the role of the flavonoids fisetin, luteolin, myricetin, and morin in inhibiting the activation of mitogen-activated protein kinase (MAPK) and AKT as well as their role in lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) transcription. All four of these flavonoids were found to inhibit MAPK and AKT. Fisetin and luteolin blocked the activation of MAPK and AKT to levels below basal levels. All of these flavonoids also blocked LPS-mediated COX-2 expression.
