Chemically-Modified-Curcumin (CMC 2.24): A Novel Therapeutic for Experimental Periodontitis

Objectives: To determine the efficacy of triketonic CMC2.24 in modulating the host-response, including alveolar bone loss, in a therapeutic model of rat periodontitis.
Methods: Thirty adult male Sprague Dawley rats were distributed into two experiments (I and II). Periodontitis was induced by repeated gingival injections of E. Coli LPS for 3 or 4 weeks; PBS was injected into the gingiva of the control group. After experimental periodontitis was established, CMC2.24 (30mg/kg) was orally administered daily for 1 week (I) or 2 weeks (II). The rats were sacrificed and gingival tissue, blood, and jaws collected. Alveolar bone loss was measured morphometrically and radiographically. Gingival extracts and plasma were analyzed for matrix metalloproteinases (MMP-2 and MMP-9) by scanning gelatin zymograms, and cytokines measured by ELISA.
Results: Both 1-week (I) and 2-week (II) CMC 2.24 therapy reduced pro and active forms of MMP-2 and MMP-9 in gingival tissue (however, MMP-9 was more responsive than MMP-2), and reduced alveolar bone loss between first and second molars (P<0.05). However, pro-inflammatory cytokines (IL-β, IL-6, and TNF-α) were not significantly affected in gingiva or plasma.
Conclusions: Systemic (oral route) administration of CMC 2.24 in rats with actively-destructive periodontitis “normalized” (i) pathologically-excessive levels of gingival MMPs, and (ii) alveolar bone loss in a therapeutic rat model. These data indicate significant potential of this safe compound to treat already-established periodontitis; evidence of efficacy is also available for other chronic inflammatory diseases.