4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and periodontal inflammation.
Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs). This ultimately results in the destruction of periodontal connective tissues including alveolar bone. Curcumin is the principal dyestuff in the popular Indian spice turmeric and has significant regulatory effects on inflammatory mediators but is characterized by poor solubility and low bioactivity. Recently, we developed a series of chemically modified curcumins (CMCs) with increased solubility and zinc-binding activity, while retaining, or further enhancing, their therapeutic effects. In the current study, we demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin) has significant inhibitory effects, better than the parent compound curcumin, on proinflammatory cytokines and MMPs in in vitro, in cell culture, and in an animal model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its congeners may help to prevent tissue damage during various chronic inflammatory diseases including periodontitis and may reduce the risks of systemic diseases associated with this local disorder.
Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8706, USA.
Ying
Y
Gu
Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Hsi-Ming
HM
Lee
Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8706, USA.
Nicole
N
Napolitano
Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8706, USA.
McKenzie
M
Clemens
Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Yazhou
Y
Zhang
Department of Oral and Maxillofacial Diseases, Institute of Dentistry, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Timo
T
Sorsa
Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
Yu
Y
Zhang
Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA ; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Francis
F
Johnson
Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Lorne M
LM
Golub
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D036381:Diarylheptanoids; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010518:Periodontitis / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C000592345:4-methoxycarbonyl curcumin; D000893:Anti-Inflammatory Agents; D036381:Diarylheptanoids; D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D003474:Curcumin