Oral supplementation with p-coumaric acid protects mice against diabetes-associated spontaneous destruction of periodontal tissue

Objective: Dietary bioactive materials having anti-inflammatory and antioxidant potentials are able to inhibit diabetes-associated periodontal complications. Although numerous studies indicate that administration of p-coumaric acid (p-CA) ameliorates diabetes and diabetes-related complications, the roles of p-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 p-CA protects mice against diabetes-associated spontaneous periodontal destruction and also explored the associated mechanism therein using in vivo and in vitro experimental systems.

Materials and methods: 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 p-CA (50 mg/kg) (STZ+CA group) or with buffer only (STZ group) daily for 6 weeks. The effect of p-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 p-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.

Results: 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 p-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 p-CA.

Conclusion: These findings demonstrate that supplementation with p-CA inhibits diabetes-associated spontaneous destruction of periodontal tissue by enhancing anti-inflammatory, anti-osteoclastogenic, and antioxidant defense systems in STZ-treated mice.