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

Abstract

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/βcatenin 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.

Resveratrol attenuates advanced glycation end product-induced senescence and inflammation in human gingival fibroblasts

“…1 ). Studies have demonstrated that AGEs-induced oxidative stress leads to chronic inflammation 27 , 28 and RES has anti-oxidant activity, 24 thus we utilize DCFH-DA to investigate the formation of ROS. Results showed that AGEs significantly increased the production of ROS and administration of RES significantly suppressed ROS production ( Fig.…”

“… 23 Resveratrol has also been shown to diminish inflammation and oxidative stress by inhibiting PI3K/Akt and WNT/β-catenin signaling pathway in LPS-induced HGFs. 24 Therefore, we further investigated whether resveratrol has the potential to decrease AGEs-mediated senescence in gingival fibroblasts. This study aimed to explore the effect and molecular mechanisms of resveratrol on AGEs-induced inflammaging in HGFs.…”

Emerging Effects of Resveratrol Derivatives in Cells Involved in Oral Wound Healing: A Preliminary Study

“…This study started from the evidence that RSV exerts beneficial effects on different cell types that are involved in the oral wound healing process. However, its limited bioavailability restricts its use as a pharmacological agent [ 29 , 30 , 31 ]. These limits drove us to synthetize sulfonamide RSV derivatives 1a – j [ 12 , 22 ] and to investigate their effects on human cells to verify their ability to improve and promote the cellular activities of HUVECs, HGFs, and HOBs.…”

Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress

“…It may be partly because resveratrol can act on various targets. Regarding the anti-inflammatory effects of resveratrol ( Baur and Sindair, 2006 ), the PI3K pathway ( Li et al, 2021 ), and the SIRT1/NRF2 signaling pathway ( Nie et al, 2020 ) are also involved. It was previously reported that SIRT1 activation inhibited ROS-associated NLRP3 inflammasome activation and ameliorates cardiac pyroptosis during myocardial I/R injury through Akt-PDH signaling pathway ( Han Y et al, 2020 ).…”