Objective To investigate the therapeutic effect of naringenin on periodontitis in rats by regulating the cyclic GMP-AMP synthetase(cGAS)/stimulator of interferon genes(STING)signaling pathway.Methods Periodontitis model was established by ligation of bilateral maxillary first molars in SD rats,and the rats were randomly divided into model group,naringin 50,100 mg/kg groups,and naringin 100 mg/kg+RocA 0.67 mg/kg group,with 10 rats in each group,and 10 normal rats were selected as control group without treatment.The symptoms of periodontitis in rats were observed and their alveolar bone was scanned with Micro CT.The probing depth(PD),gingival sulcus bleeding index(SBI),alveolar bone resorption,bone density,bone volume fraction,and trabecular bone number were evaluated in each group.HE and TRAP stainings were applied to detect the pathological morphology,inflammatory cell count,and alveolar bone osteoclast count of rat periodontal tissue,respectively.Enzyme linked immunosorbent assay(ELISA)was applied to measure the levels of inflammatory factors C reactive protein(CRP),IL-8 and,IL-6 in serum and periodontal tissue of rats in each group.Immunoblotting was applied to detect the expression of cGAS/STING pathway proteins in the periodontal tissues of rats in each group.Results Compared with control group,the PD,SBI,alveolar bone resorption,inflammatory cell count,osteoclast count,serum and periodontal tissue CRP,IL-6,IL-8 levels,cGAS and STING protein expression in the model group were obviously increased,but the bone density,bone volume fraction,and number of trabeculae were obviously decreased(P<0.05).Compared with model group,the PD,SBI,alveolar bone resorption,inflammatory cell count,osteoclast count,serum and periodontal tissue CRP,IL-6,IL-8 levels,cGAS and STING protein expression in the each dose of naringenin groups were all reduced,while the alveolar bone density,bone volume fraction,and number of trabeculae were increased(P<0.05),and it was dose-dependent.Compared with naringenin 100 mg/kg group,naringenin+RocA group showed an increase in PD,SBI,alveolar bone resorption,inflammatory cell count,osteoclast count,serum and periodontal tissue CRP,IL-6,IL-8 levels,cGAS and STING protein expression,and a decease in alveolar bone density,bone volume fraction,and number of trabeculae(P<0.05).Conclusion Naringenin can inhibit inflammation in periodontitis rats by reducing cGAS/STING signaling activity,thereby reducing periodontal tissue damage,alleviating alveolar bone resorption,repairing bone microstructure,and ultimately improving clinical symptoms.