A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis

Abstract

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.

Impact of natural curcumin on the progression of experimental periodontitis in diabetic rats

“…Diabetes mellitus and periodontitis are complex chronic diseases with an established higher risk for the development periodontitis and future tooth loss in the presence of DM . CURC is a natural compound with promising effects in modulating the osteo‐immune‐inflammatory and antioxidant host response both in periodontally diseased sites and in diabetes and related complications . For the first time, this investigation assessed the natural curcumin's impact on the progression of EP in rats induced to DM.…”

“…The outcomes of the morphometric evaluations of the current study revealed that DM induction promoted higher periodontal disease progression and that diabetic rats treated with daily CURC + INS, as well as those Non‐DM, presented lower linear bone loss values in periodontitis sites, suggesting that the combined use of CURC and INS, and not the substances used alone, may positively influence periodontal breakdown, even in the presence of DM. Although promising effects of natural CURC on periodontal tissues have already been revealed in earlier experimental and also clinical studies, only few information is available concerning the influence of a chemically modified CURC on periodontitis in the presence of a recognized at‐risk condition as diabetes mellitus and there are no data revealing the impact of a natural CURC in the progression of EP associated with DM. Of importance, although some evidence has suggested that certain chemically modified CURC shows improved solubility and bioavailability in comparison with natural CURC, advantages related to the natural form of CURC include the facility to obtain the substance and greater possibility of using this therapeutic agent for clinical application in the future.…”

“…However, no data are available concerning the impact of natural CURC in the host response related to periodontitis in the presence of diabetes. In this regard, recently, Elburki et al studies evaluated the use of a chemically modified CURC (oral gavage of 30 mg/kg, during 3 weeks) to manage EP in a rat model of diabetes. According to the authors, gingival tissue with periodontitis from animals treated with a chemically modified CURC revealed reduction of the pathologically excessive levels of matrix metalloproteinase (MMP)‐2, MMP‐8, and MMP‐9 and also decreased concentrations of TNF‐α, IL‐6, and IL‐1β0 .…”

“…In this regard, recently, Elburki et al studies evaluated the use of a chemically modified CURC (oral gavage of 30 mg/kg, during 3 weeks) to manage EP in a rat model of diabetes. According to the authors, gingival tissue with periodontitis from animals treated with a chemically modified CURC revealed reduction of the pathologically excessive levels of matrix metalloproteinase (MMP)‐2, MMP‐8, and MMP‐9 and also decreased concentrations of TNF‐α, IL‐6, and IL‐1β0 . Nevertheless, these studies did not compare the effectiveness of CURC alone with the adjunctive role of CURC in combination with INS, as performed in the current investigation, making difficult comparisons.…”

“…It has also been reported as an efficient antioxidant agent, protecting innumerous organs from oxidative stress‐induced pathophysiology . Because of its anti‐inflammatory and antioxidant properties, natural or chemically modified curcumin has also been considered as a promising therapeutic option for diabetes and related complications, as periodontitis …”