Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

• Published in: European journal of pharmacology Vol. 750; pp. 141 - 150
• Main Authors: Rufino, Ana Teresa, Ribeiro, Madalena, Sousa, Cátia, Judas, Fernando, Salgueiro, Lígia, Cavaleiro, Carlos, Mendes, Alexandrina Ferreira
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-03-2015
• Subjects: Adult; Aged; Aggrecans - genetics; Alkenes - pharmacology; Anabolic Agents - pharmacology; Anti-Inflammatory Agents - pharmacology; Chondrocytes - drug effects; Chondrocytes - enzymology; Chondrocytes - metabolism; Chronic inflammation; Collagen Type I - genetics; Collagen Type II - genetics; Cyclohexenes - pharmacology; Enzyme Activation - drug effects; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Humans; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - pharmacology; MAPK; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 13 - genetics; Middle Aged; Mitogen-Activated Protein Kinases - metabolism; Monoterpenes - pharmacology; Natural products; NF-kappa B - metabolism; NF-κB; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - genetics; Osteoarthritis; Osteoarthritis - pathology; Sesquiterpenes - pharmacology; Terpenes - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-3 - genetics; Young Adult; NF-κB; MAPK; Chronic inflammation; Natural products; Osteoarthritis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2015.01.018

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-1β-induced nitric oxide production (IC50=37.3μg/ml and 85.3µg/ml, respectively), but E-caryophyllene was inactive. Myrcene, and limonene to a lesser extent, also decreased IL-1β-induced NF-κB, 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-1β-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-1β. 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.
[Display omitted]