Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 750, Issue -, Pages 141-150Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2015.01.018
Keywords
Osteoarthritis; Chronic inflammation; NF-kappa B; MAPK; Natural products
Categories
Funding
- FEDER (QREN), through Programa Mais Centro [CENTRO-07-ST24-FEDER-002006]
- FEDER (QREN), through Programa Operacional Factores de Competitividade - COMPETE
- FCT - Fundacao Portuguesa para a Ciencia e a Tecnologia [PestC/SAU/LA0001/20132014, Pest-OE/SAU/U10177/2011, PTDC/EME-TME/113039/2009, SFRH/BD/47470/2008, SFRH/BD/78188/2011, SFRH/BD/79600/2011]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/78188/2011, SFRH/BD/79600/2011, SFRH/BD/47470/2008, PTDC/EME-TME/113039/2009] Funding Source: FCT
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Osteoarthritis is a progressive joint disease and a major cause of disability for which no curative therapies are yet available. To identify compounds with potential anti-osteoarthritic properties, in this study, we screened one sesquiterpene, E-caryophyllene, and two monoterpenes, myrcene and limonene, hydrocarbon compounds for anti-inflammatory, anti catabolic and pro anabolic activities in human chondrocytes. At non-cytotoxic concentrations, myrcene and limonene inhibited IL-1 beta-induced nitric oxide production (IC50=37.3 mu g/ml and 85.3 mu g/ml, respectively), but E-caryophyllene was inactive. Myrcene, and limonene to a lesser extent, also decreased IL-1 beta-inclucecl NF-kappa B, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, while increasing the expression of anti-catabolic genes (TIMP-1 and -3 by myrcene and TIMP-1 by limonene). Limonene increased ERK1/2 activation by 30%, while myrcene decreased it by 26%, relative to IL-1 beta-treated cells. None of the compounds tested was able to increase the expression of cartilage matrix-specific genes (collagen II and aggrecan), but both compounds prevented the increased expression of the non-cartilage specific, collagen I. induced by IL-1 beta. These data show that myrcene has significant anti-inflammatory and anti-catabolic effects in human chondrocytes and, thus, its ability to halt or, at least, slow down cartilage destruction and osteoarthritis progression warrants further investigation. (C) 2015 Elsevier B.V. All rights reserved.
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