title: A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations.
abstract: Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or μ-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations.
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Muna S
authors.initials: MS
authors.lastname: Elburki
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, 14801-903 Araraquara, SP, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rossa
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, 14801-903 Araraquara, SP, Brazil.
authors.forename: Morgana R
authors.initials: MR
authors.lastname: Guimaraes
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Goodenough
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Hsi-Ming
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, 14801-903 Araraquara, SP, Brazil.
authors.forename: Fabiana A
authors.initials: FA
authors.lastname: Curylofo
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Johnson
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Lorne M
authors.initials: LM
authors.lastname: Golub
mesh_terms: D000818:Animals; D003474:Curcumin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D010510:Periodontal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D003474:Curcumin
references.citation: J Appl Oral Sci. 2010 Sep-Oct;18(5):493-7
references.pmid: 21085806
references.citation: Biochem Biophys Res Commun. 2005 Oct 7;335(4):1017-25
references.pmid: 16102725
references.citation: J Periodontol. 2004 Mar;75(3):453-63
references.pmid: 15088884
references.citation: Nat Rev Drug Discov. 2007 Jun;6(6):480-98
references.pmid: 17541420
references.citation: J Periodontal Res. 2011 Apr;46(2):269-79
references.pmid: 21306385
references.citation: PLoS One. 2013 Sep 24;8(9):e69884
references.pmid: 24086245
references.citation: Pharmacol Res. 2011 Dec;64(6):624-9
references.pmid: 21782948
references.citation: Crit Rev Oral Biol Med. 1991;2(3):297-321
references.pmid: 1654139
references.citation: J Periodontal Res. 1983 Jan;18(1):23-30
references.pmid: 6304279
references.citation: J Immunol. 2004 May 15;172(10):5940-7
references.pmid: 15128775
references.citation: Mediators Inflamm. 2013;2013:329740
references.pmid: 24453415
references.citation: Adv Dent Res. 1998 Nov;12(2):12-26
references.pmid: 9972117
references.citation: J Dent Res. 2010 Jun;89(6):644-9
references.pmid: 20348487
references.citation: J Appl Oral Sci. 2012 Mar-Apr;20(2):128-38
references.pmid: 22666826
references.citation: Biochem Pharmacol. 2007 May 1;73(9):1434-45
references.pmid: 17291458
references.citation: Curr Med Chem. 2012;19(25):4348-58
references.pmid: 22830350
references.citation: J Oral Microbiol. 2012;4:
references.pmid: 23071896
references.citation: Inflamm Res. 1997 Aug;46(8):310-9
references.pmid: 9297576
references.citation: Innate Immun. 2012 Feb;18(1):155-63
references.pmid: 21242275
references.citation: J Pharmacol Exp Ther. 2008 Jul;326(1):196-208
references.pmid: 18417733
references.citation: J Am Dent Assoc. 2011 Mar;142(3):262-73
references.pmid: 21357860
references.citation: Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):733-8
references.pmid: 14962945
references.citation: Curr Opin Rheumatol. 1999 May;11(3):202-9
references.pmid: 10328580
references.citation: Cancer Lett. 2004 Aug 10;211(2):235-42
references.pmid: 15219947
references.citation: J Inflamm (Lond). 2012 Oct 01;9(1):35
references.pmid: 23025537
references.citation: Ann N Y Acad Sci. 1994 Sep 6;732:96-111
references.pmid: 7978855
references.citation: J Clin Periodontol. 1995 Feb;22(2):100-9
references.pmid: 7775665
references.citation: Life Sci. 2009 May 22;84(21-22):745-54
references.pmid: 19285515
references.citation: Acta Biochim Pol. 2012;59(2):201-12
references.pmid: 22590694
references.citation: Curr Med Chem. 2012;19(25):4367-75
references.pmid: 22830351
references.citation: Nat Rev Immunol. 2008 May;8(5):349-61
references.pmid: 18437155
references.citation: Clin Exp Immunol. 2006 Aug;145(2):313-21
references.pmid: 16879252
references.citation: Pharmacol Res. 2011 Feb;63(2):121-9
references.pmid: 20937388
references.citation: Ann Med. 2006;38(5):306-21
references.pmid: 16938801
references.citation: Nat Rev Cancer. 2002 Sep;2(9):657-72
references.pmid: 12209155