Background: Implants are commonly used to repair teeth. However, with their widespread use, the incidence of peri-implantitis has also increased. The Mitogen activated protein kinase/Protein kinase B/Nuclear factor kappa-B (MAPK/AKT/NF-κB) signaling pathway is associated with various inflammatory responses. This study aims to evaluate the role of resveratrol in managing peri-implant inflammation and its regulatory effect on the MAPK/AKT/NF-κB signaling pathway.

Methods: Peri-implant bone loss was measured by micro-computed tomography, and gingival cell apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The levels of apoptosis-related proteins (caspase-3, B-cell lymphoma-2 (Bcl-2)), inflammation-related proteins (caspase-1, phospho-p65 (p-p65)/p65), and MAPK/AKT/NF-κB signaling pathway-related proteins (p38 MAPK, AKT, and NF-κB) in inflammatory tissue were determined by western blotting. Enzyme-linked immunosorbent assay was used to measure the levels of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), IL-1β, IL-4, and IL-10 in the serum of mice. Biochemical kits were used to measure the levels of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) in inflammatory tissue. The intercellular reactive oxygen species (ROS) content was detected by ROS staining, and the morphology of inflammatory tissue was observed by hematoxylin-eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining.

Results: The administration of resveratrol significantly reduced bone loss around the implant and prevented the apoptosis of gingival cells (p < 0.001). Additionally, resveratrol effectively reduced the concentration of serum inflammatory factors and inflammation-related proteins, namely caspase-1 and p-p65/p65 (p < 0.001). Additionally, in the resveratrol intervention group, the contents of MDA and NO, and the level of ROS decreased, while the content of SOD increased (p < 0.05). The HE, immunofluorescence, and TRAP staining results confirmed that resveratrol effectively reduced the number of total inflammatory cells in gingival tissue (p < 0.05).

Conclusion: Resveratrol has the potential to alleviate peri-implant inflammation and regulate the MAPK/AKT/NF-κB signaling pathway. This offers a novel approach for drug-based clinical interventions in peri-implant inflammation.