Resveratrol prevents inflammation and oxidative stress response in LPS-induced human gingival fibroblasts by targeting the PI3K/AKT and Wnt/β-catenin signaling pathways

This study aimed to elucidate the anti-inflammatory and antioxidant properties of resveratrol (RSV) in human gingival fibroblasts (HGFs) following stimulation by P. gingivalis lipopolysaccharide (LPS). The levels of the inflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, the activity of the antioxidant enzymes SOD and GSH-Px, and the levels of MDA, were evaluated by ELISA. It was observed that the expression of IL-1β, IL-6, IL-8 and TNFα in LPS-induced HGFs was significantly downregulated by RSV in a dose-dependent manner. RSV also partly increased oxidative stress (OS)-related factors, including SOD and GSH-Px, which was accompanied by a decrease in MDA production, although the results were not statistically significant. Additionally, RSV-induced deactivation of the PI3K/AKT and Wnt/β-catenin pathways in LPS-induced HGFs was observed by western blot analysis. Subsequently, it was demonstrated treatment with PI3K/AKT pathway inhibitor (LY294002) or Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1) could further enhance the anti-inflammatory and antioxidant effects of RSV by downregulating the expression of IL-1β, IL-6, IL-8 and TNFα, and the production of MDA, and increasing the activity of SOD and GSH-Px in LPS-induced HGFs. These results suggested RSV attenuated the inflammation and OS injury of P. gingivalis LPS-treated HGFs by deactivating the PI3K/AKT and Wnt/β-catenin signaling pathways.