Department of Periodontics, Faculty of Dentistry, University of Benghazi, Jamal Abdel Nasser Street, Benghazi, Libya.
Department of Diagnosis and Surgery, School of Dentistry at Araraquara-UNESP, Araraquara, Brazil.
Inflammation. 2017 Aug;40(4):1436-1449. doi: 10.1007/s10753-017-0587-4.
The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.
本研究旨在评估新型化学修饰姜黄素（CMC 2.24）对两种大鼠牙周病实验模型中 NF-κB 和 MAPK 信号通路及炎症细胞因子产生的影响。实验模型 I：通过向牙龈内重复注射 LPS（每周 3 次，持续 3 周）诱导牙周炎；对照组大鼠给予载体注射。CMC 2.24 或载体通过每日口服灌胃给药 4 周。实验模型 II：成年雄性大鼠通过链脲佐菌素注射诱导糖尿病；随后，由于高血糖控制不佳，导致牙周破坏。非糖尿病大鼠作为对照。糖尿病大鼠给予 CMC 2.24 或载体通过口服灌胃给药 3 周。采集上颌骨和牙龈组织，并用 X 射线评估骨丢失。根据实验条件将牙龈组织汇集，并进行基质金属蛋白酶（MMPs）和破骨细胞因子分析。通过 Western blot 评估 p38 MAPK 和 NF-κB 信号通路的激活情况。LPS 和糖尿病均在上皮组织中诱导炎症过程，与牙槽骨过度吸收和 p65（NF-κB）和 p38 MAPK 过度激活相关。在两种模型中，CMC 2.24 的给药均可在上皮组织中产生明显减少炎症细胞因子和 MMPs、减少骨丢失和减少 p65（NF-κB）和 p38 MAPK 激活的作用。这种新型三酮姜黄素（天然姜黄素为二酮）对这些细胞信号通路的抑制作用可能在其局部和全身相关牙周炎的治疗效果中发挥作用。
