ABSTRACT
Periodontitis is a highly prevalent infective and inflammatory disease with an adverse impact on systemic health. Isorhamnetin, a flavonoid mainly isolated from Hippophae fhamnoides L. fruit, has been reported to have anti-inflammatory effect. This study aimed to investigate the anti-inflammatory effects and mechanism of isorhamnetin on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). The production of inflammatory mediators and the expression of proteins were measured by ELISA and western blot analysis. The results demonstrated that isorhamnetin attenuated LPS-induced release of PGE2, NO, IL-6, and IL-8 in HGFs. Isorhamnetin also inhibited LPS-induced NF-κB activation. The expression of Nrf2 and HO-1 were up-regulated by treatment of isorhamnetin. Furthermore, knockdown of Nrf2 by siRNA reversed the anti-inflammatory effects of isorhamnetin. In conclusion, these results suggested that isorhamnetin inhibited LPS-induced inflammation in HGFs by activating Nrf2 signaling pathway.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gingiva/metabolism , Lipopolysaccharides/adverse effects , NF-E2-Related Factor 2/metabolism , Quercetin/analogs & derivatives , Signal Transduction/drug effects , Cell Survival/drug effects , Dinoprostone/metabolism , Heme Oxygenase-1/metabolism , Humans , Inflammation/drug therapy , Interleukin-6/metabolism , Interleukin-8/metabolism , NF-kappa B/metabolism , Periodontitis , Quercetin/pharmacologyABSTRACT
Icariin (ICA), a flavanoid isolated from herbal Epimedium, has multiple biological activities. The present study investigated the effects of ICA on the proliferation and alkaline phosphatase (ALP) activity (an index for PDLC differentiation) of human periodontal ligament cells (hPDLCs) inhibited by lipopolysaccharide (LPS). hPDLCs were cultured in vitro and stimulated with various concentrations of ICA. The proliferation ability of hPDLCs was detected by an MTT assay. The activity of ALP was determined by the p-Nitrophenyl phosphate method, and the expression of ALP was analyzed by reverse transcription polymerase chain reaction and western blot analysis. ICA exhibited a dose-dependent effect on the proliferation of hPDLCs in a suitable concentration range, from 10-6 to 10-8 mol/l, and with a mediate optimal concentration (10-6 mol/l). The alkaline phosphatase activity was markedly inhibited in 10 µg/ml LPS-treated PDLCs and this inhibition was suppressed in the presence of icariin at a concentration of 10-6 mol/L following prolonged treatment (96 h). Therefore, this study provided insight into the use of ICA for periapical tissue regeneration.