Resveratrol treats peri-implantitis in mice via inhibiting the MAPKs/NF-κB signaling pathway

Abstract

Objective To investigate the effect of resveratrol (RSV) in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B (NF-κB) signaling and mitogen-activated protein kinase (MAPKs) signaling. Methods This study has been reviewed and approved by the Ethics. After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks, implants were implanted at the site of the first molar. The mice were randomly divided into a control group, a mouse peri implantitis model group, a low-dose group of 20 mg/kg resveratrol (RSV-L), and a high-dose group of 40 mg/kg resveratrol (RSV-H). After 4 weeks of implant implantation, a silk thread ligation induced peri implantitis model was established in all mice except for the control group. The model group received intervention with physiological saline by gavage, while the drug group received intervention with resveratrol by gavage for 6 consecutive weeks. After 6-week treatment, observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in gingival crevicular fluid. HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants. Protein expression level and phosphorylation level of extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen activated protein kinase (p38 MAPK), p-p38MAPK, nuclear factor kappa-B (NF-κB), p-NF-κB, nuclear factor-κB inhibitory protein (IκΒα), p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot (WB). Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorption. Among them, the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group. The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites: proximal, distal, buccal, and palatal. High dose resveratrol intervention reduced alveolar bone resorption (P<0.05); compared with the low-dose group, the high-dose group showed a decrease in palatal bone resorption (P<0.05), while there was no significant difference in absorption between the mesial, distal, and buccal sides (P>0.05). The ELISA results showed that compared with the model group, the levels of TNF - α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower (P<0.05). The IL-6 in the gingival crevicular fluid of mice in the high-dose resveratrol group was lower than that in the low-dose group (P<0.05). However, there was no significant difference in TNF-α levels between the two groups. HE staining showed a decrease in inflammatory cell infiltration in mice after treatment with resveratrol. The WB results showed that compared with the control group, the expression levels of p-Erk, p-JNK, p-p38MAPK, p-IκA, and p-NF-κB phosphorylated proteins in the gingival tissue of the model group mice were significantly increased (P<0.01). The resveratrol treatment group significantly inhibited the phosphorylation of p-Erk, p-JNK, p-p38MAPK, p-IκA, and p-NF-κB proteins. Compared with the low-dose group, the high-dose group inhibited the phosphorylation of MAPKs/NF-κB signaling pathway related proteins more significantly (P<0.05). Conclusion Resveratrol protect ligature induced peri-implantitis murine model, which may be related to its inhibition of phosphorylation of MAPKs/NF-κB pathway.

Keywords

• peri-implantitis|resveratrol|animal model|p38 mitogen activated protein kinase|nuclear factor kappa-b