Protective effect of Nrf2 in periodontitis – A preclinical systematic review and meta-analysis

Periodontitis is an inflammatory disease, while Nuclear factor erythroid-2 related factor 2 (Nrf2) acts a significant part in antioxidant, anti-inflammatory and immune response. However, the evidence in preclinical studies to certify Nrf2 can slow down the progression of periodontitis or facilitate its recovery is not enough. The present report aims to investigate the functional implications of Nrf2 in animal periodontitis models by evaluating the changes of Nrf2 levels and analyzing the clinical benefits of Nrf2 activation in the same models.We searched PubMed, Web of Science, EBSCO, CNKI, VIP, Wan Fang databases. The random-effects model was used to evaluate the mean differences (MD) and 95 % confidence intervals (95%CI) when the units of measurements of outcome indicators were the same, in contrast, the standardized mean differences (SMD) and 95%CI were evaluated while the units were different.8 studies were included for quantitative synthesis. Compared with healthy groups, the expression of Nrf2 was markedly lower in periodontitis groups (SMD: -3.69; 95%CI: -6.25, -1.12). After administration of kinds of Nrf2-activators, a significant increase in Nrf2 levels (SMD: 2.01; 95%CI: 1.27, 2.76) was accompanied by a decrease in distance between cementoenamel junction and alveolar bone crest (CEJ-ABC) (SMD: -2.14; 95%CI: -3.29, -0.99) and an improvement of bone volume/tissue volume (BV/TV) (SMD:17.51; 95%CI: 16.24, 18.77) was evaluated compared with periodontitis groups.Nrf2 has a certain protective effect on periodontitis, however, the specific role Nrf2 plays in the development and severity of periodontitis remains to be demonstrated. PROSPERO registration number: CRD42022328008.