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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

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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.

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Acknowledgements

This study was supported by Grant no. A43273 from the New York State Office of Science, Technology, and Academic Research (NYSTAR), through NYSTAR’s Center of Advanced Technology, and a Grant (A37298) from the Research Foundation, Stony Brook University, and Sao Paulo State Research Foundation (FAPESP) Grant nos. 2009/54080-0, 2010/20091-2, 2010/19660-2, and 2012/15826-9, and from the Ministry of Higher Education and Scientific Research in Libya.

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Authors and Affiliations

  1. Department of Periodontics, Faculty of Dentistry, University of Benghazi, Jamal Abdel Nasser Street, Benghazi, Libya

    Muna S. Elburki

  2. Department of Diagnosis and Surgery, School of Dentistry at Araraquara—UNESP, Araraquara, Brazil

    Carlos Rossa Jr, Morgana R. Guimarães-Stabili & Fabiana A. Curylofo-Zotti

  3. Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook, Stony Brook, NY, USA

    Hsi-Ming Lee & Lorne M. Golub

  4. Department of Chemistry and Pharmacological Sciences, SUNY at Stony Brook, Stony Brook, NY, USA

    Francis Johnson

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  1. Muna S. Elburki
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  2. Carlos Rossa Jr
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  3. Morgana R. Guimarães-Stabili
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  4. Hsi-Ming Lee
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  5. Fabiana A. Curylofo-Zotti
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  6. Francis Johnson
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  7. Lorne M. Golub
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Corresponding author

Correspondence to Muna S. Elburki.

Ethics declarations

The study protocol was previously approved by the Institution’s Committees (Araraquara-UNESP, SP, Brazil, and Stony Brook University, NY, USA) for Experimental Animal Use.

Conflict of Interests

Lorne M. Golub is listed as an inventor on several related patents, and these have been fully assigned to his institution, Stony Brook University, State University of New York (SUNY). Francis Johnson is also listed as an inventor on several related patents which have been fully assigned to Stony Brook University and to Chem-Master Int., Inc., on a shared basis. He declares that he has no conflict of interests, financial or otherwise, with regard to the publication of this paper. All other authors declare that there is no conflict of interest regarding the publication of this paper.

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Elburki, M.S., Rossa, C., Guimarães-Stabili, M.R. et al. 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. Inflammation 40, 1436–1449 (2017). https://doi.org/10.1007/s10753-017-0587-4

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  • DOI: https://doi.org/10.1007/s10753-017-0587-4

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