Oral supplementation with <i>p</i>‐coumaric acid protects mice against diabetes‐associated spontaneous destruction of periodontal tissue

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Dietary bioactive materials having anti‐inflammatory and antioxidant potentials are able to inhibit diabetes‐associated periodontal complications. Although numerous studies indicate that administration of <jats:italic>p</jats:italic>‐coumaric acid (<jats:italic>p</jats:italic>‐CA) ameliorates diabetes and diabetes‐related complications, the roles of <jats:italic>p</jats:italic>‐CA on periodontal tissue destruction in diabetic mice and the possible mechanisms therein are not completely understood. In this study, we evaluated whether supplementation with <jats:italic>p</jats:italic>‐CA protects mice against diabetes‐associated spontaneous periodontal destruction and also explored the associated mechanism therein using in vivo and in vitro experimental systems.</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>C57BL/6 male mice were divided into sham, streptozotocin (STZ), and STZ+CA groups (n = 5/group). Sham group was intraperitoneally injected with sodium buffer, whereas other two groups were injected with the buffer containing 160 mg/kg of STZ. STZ‐induced diabetic mice received oral gavage with <jats:italic>p</jats:italic>‐CA (50 mg/kg) (STZ+CA group) or with buffer only (STZ group) daily for 6 weeks. The effect of <jats:italic>p</jats:italic>‐CA on diabetes‐associated spontaneous periodontal destruction was evaluated using μCT analysis, hematoxylin and eosin staining, tartrate‐resistant acid phosphatase staining, and immunohistochemical staining methods. The efficacies of <jats:italic>p</jats:italic>‐CA on cell proliferation, osteoblast differentiation, reactive oxygen species (ROS) accumulation, and antioxidant‐related marker expression were examined using human periodontal ligament fibroblasts (hPLFs) cultured under high glucose condition.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Streptozotocin group exhibited periodontal tissue destruction along with increased inflammation, oxidative stress, and osteoclast formation, as well as with decreased osteogenesis. However, oral administration with <jats:italic>p</jats:italic>‐CA protected mice against STZ‐induced periodontal destruction by inhibiting inflammation and osteoclastic activation. STZ+CA group also showed higher expression of antioxidant and osteogenic markers in periodontal tissue than did STZ group. Treatment with high glucose concentration (30 mmol/L) impaired proliferation and osteoblast differentiation of hPLFs along with cellular ROS accumulation, whereas these impairments were almost completely disappeared by supplementation with <jats:italic>p</jats:italic>‐CA.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These findings demonstrate that supplementation with <jats:italic>p</jats:italic>‐CA inhibits diabetes‐associated spontaneous destruction of periodontal tissue by enhancing anti‐inflammatory, anti‐osteoclastogenic, and antioxidant defense systems in STZ‐treated mice.</jats:p></jats:sec>