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 mononu...

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Main Authors: Ying Gu, Hsi-Ming Lee, Nicole Napolitano, McKenzie Clemens, Yazhou Zhang, Timo Sorsa, Yu Zhang, Francis Johnson, Lorne M. Golub
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/329740
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author Ying Gu
Hsi-Ming Lee
Nicole Napolitano
McKenzie Clemens
Yazhou Zhang
Timo Sorsa
Yu Zhang
Francis Johnson
Lorne M. Golub
author_facet Ying Gu
Hsi-Ming Lee
Nicole Napolitano
McKenzie Clemens
Yazhou Zhang
Timo Sorsa
Yu Zhang
Francis Johnson
Lorne M. Golub
author_sort Ying Gu
collection DOAJ
description 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.
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institution Kabale University
issn 0962-9351
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language English
publishDate 2013-01-01
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series Mediators of Inflammation
spelling doaj-art-3f746242d3d6447796df531c900bcbd12025-02-03T06:07:55ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/3297403297404-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal InflammationYing Gu0Hsi-Ming Lee1Nicole Napolitano2McKenzie Clemens3Yazhou Zhang4Timo Sorsa5Yu Zhang6Francis Johnson7Lorne M. Golub8Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8706, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8706, USADepartment of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8706, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of Oral and Maxillofacial Diseases, Institute of Dentistry, Helsinki University Central Hospital, University of Helsinki, Helsinki, FinlandDepartment of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USADepartment of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USAChronic 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.http://dx.doi.org/10.1155/2013/329740
spellingShingle Ying Gu
Hsi-Ming Lee
Nicole Napolitano
McKenzie Clemens
Yazhou Zhang
Timo Sorsa
Yu Zhang
Francis Johnson
Lorne M. Golub
4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation
Mediators of Inflammation
title 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation
title_full 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation
title_fullStr 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation
title_full_unstemmed 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation
title_short 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation
title_sort 4 methoxycarbonyl curcumin a unique inhibitor of both inflammatory mediators and periodontal inflammation
url http://dx.doi.org/10.1155/2013/329740
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