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

Abstract

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.

Association among serum and salivary A. actinomycetemcomitans specific immunoglobulin antibodies and periodontitis

“…Some of the major issues associated with PT were the tissue hypoxia, oxidative stress and relative vasospasm which in turn, determines increased coagulation and endothelial injury, damage of vascular endothelial cells, and finally periodontal tissue destruction [ 44 ]. Consequently, some evidence has been suggested that periodontal infection mediated by some pathogens such as A. actinomycetemcomitans may accelerate PT and endothelial damage and inflammatory response orchestrated through oxidative stress pathways [ 45 , 46 ], especially in obese patients [ 47 ].…”

Dietary polyphenols as antidiabetic agents: Advances and opportunities

“…Ferulic acid also increased glucokinase activity (Jung et al, 2007) and decreased glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in liver (Son, Rico, Nam, & Kang, 2011 (Pei, Ou, Huang, & Ou, 2016). The supplementation of p-coumaric acid can prevent bone loss (Yamaguchi, Uchiyama, & Lai, 2007), inhibit diabetes-associated spontaneous destruction of periodontal tissue by (Bhattarai et al, 2019), and alleviate diabetic nephropathy in diabetic animals (Zabad, Samra, & Eissa, 2019).…”

“…p ‐Coumaric acid shows antidiabetic activity by reducing the intestinal absorption of carbohydrate, modulating glucose metabolism enzymes, improving β‐cell function, stimulating insulin secretion, increasing insulin sensitivity, activating AMP‐activated protein kinase, inhibiting adipogenesis and gluconeogenesis, and enhancing antioxidant potential and anti‐inflammation effects (Pei, Ou, Huang, & Ou, 2016). The supplementation of p ‐coumaric acid can prevent bone loss (Yamaguchi, Uchiyama, & Lai, 2007), inhibit diabetes‐associated spontaneous destruction of periodontal tissue by (Bhattarai et al., 2019), and alleviate diabetic nephropathy in diabetic animals (Zabad, Samra, & Eissa, 2019).…”

Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System

“…Chronic inflammatory responses also contribute to a mild and prolonged production of ROS leading to oxidative damages to cells and tissues [13]. Similarly, periodontitis, a chronic periodontal inflammatory disease, involves an excessive ROS generation in the periodontium [14,15]. Therefore, oxidative stress might be the key mediator in DM-associated periodontal destruction, as well as in hyperglycemia-related systemic disorders.…”