{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T03:48:39Z","timestamp":1785556119335,"version":"3.56.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901019"],"award-info":[{"award-number":["81901019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870798"],"award-info":[{"award-number":["81870798"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Oxidative stress has been suggested as an important pathogenic factor contributing to chronic periodontitis with diabetes mellitus (CPDM). Previous studies have revealed the potential therapeutic properties of baicalein (BCI) in oxidative stress\u2010related diseases; however, the antioxidant effects of BCI on therapy for individual with CPDM remain largely unexplored. Nuclear factor erythroid 2\u2010related factor 2 (Nrf2) plays a critical role in cellular defence against oxidative stress. In this study, we aim to determine whether BCI prevents diabetes\u2010related periodontal tissue destruction by regulating Nrf2 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Human gingival epithelial cells (hGECs) were challenged with high glucose (HG, 25\u00a0mmol\/L) and\/or lipopolysaccharide (LPS, 20\u00a0\u00b5g\/mL). Reactive oxygen species (ROS) were detected by fluorescence\u2010activated cell sorting. The changes of antioxidant\u2010related genes, including <jats:italic>Nrf2<\/jats:italic>, catalase (<jats:italic>Cat<\/jats:italic>), glutamate\u2010cysteine ligase catalytic subunit (<jats:italic>Gclc<\/jats:italic>), superoxide dismutase 1 (<jats:italic>Sod1<\/jats:italic>)<jats:italic>,<\/jats:italic> and superoxide dismutase 2 (<jats:italic>Sod2<\/jats:italic>), were quantified by real\u2010time PCR. The localization of phospho\u2010Nrf2 (pNrf2, S40) in the nucleus was detected by immunofluorescence staining and laser scanning confocal microscope (LSCM). PNrf2 and total form of Nrf2 were determined using\u00a0western blot. The above indicators together with mitochondrial membrane potential (MMP) were further investigated in hGECs pre\u2010treated with different concentrations of BCI (0.01, 0.1, or 0.5\u00a0\u00b5g\/mL) before stimulated with HG plus LPS (GP). Finally, the role of BCI in activating Nrf2 signaling pathway and relieving the alveolar bone absorption was examined in the CPDM model of Sprague Dawley rats. CPDM rats were oral gavaged with BCI (50, 100, or 200\u00a0mg\/kg daily). The pNrf2 was detected by immunohistochemistry, and the alveolar bone absorption was examined by microcomputed tomography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that ROS were significantly increased in both groups of HG and LPS, with the strongest generation in the GP group. In terms of ROS\u2010related gene expression, we found that the mRNA levels of <jats:italic>Nrf2<\/jats:italic>, <jats:italic>Cat<\/jats:italic>, <jats:italic>Gclc<\/jats:italic>, <jats:italic>Sod1,<\/jats:italic> and <jats:italic>Sod2<\/jats:italic> were significantly decreased in HG and LPS groups. In consistent with the strongest induction of ROS in GP group, the gene expression in GP group was further decreased as compared to those of HG and LPS groups. Also, the expression of pNrf2 exhibited the same trend with the expression of those antioxidant genes. However, the generation of ROS and the loss of mitochondrial membrane potential induced by GP were abolished by pre\u2010treatment with different concentrations of BCI (0.01, 0.1, or 0.5\u00a0\u00b5g\/mL). Interestingly, we observed that BCI promoted the nucleus translocation of pNrf2, as well as the gene expression levels of pNrf2 and its target genes (<jats:italic>Cat, Gclc, Sod1, and Sod2<\/jats:italic>). Finally, in the CPDM animal model, we found that BCI (at concentrations: 50, 100, and 200\u00a0mg\/kg) markedly increased the number of pNrf2\u2010positive cells in periodontal tissue and mitigated the alveolar bone loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data revealed a potential role for clinic application of BCI under CPDM conditions, suggesting a new therapeutic drug for CPDM patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12722","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T11:12:33Z","timestamp":1576753953000},"page":"381-391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling 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