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

Eur J Pharmacol. 2015 Mar 5;750:141-50. doi: 10.1016/j.ejphar.2015.01.018. Epub 2015 Jan 23.

Abstract

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.

Keywords: Chronic inflammation; MAPK; NF-κB; Natural products; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Adult
  • Aged
  • Aggrecans / genetics
  • Alkenes / pharmacology*
  • Anabolic Agents / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Chondrocytes / drug effects*
  • Chondrocytes / enzymology
  • Chondrocytes / metabolism
  • 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
  • Limonene
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 13 / genetics
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • Monoterpenes / pharmacology*
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Osteoarthritis / pathology*
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes / pharmacology*
  • Terpenes / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Young Adult

Substances

  • Acyclic Monoterpenes
  • Aggrecans
  • Alkenes
  • Anabolic Agents
  • Anti-Inflammatory Agents
  • Collagen Type I
  • Collagen Type II
  • Cyclohexenes
  • Interleukin-1beta
  • Monoterpenes
  • NF-kappa B
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • TIMP1 protein, human
  • Terpenes
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-3
  • Nitric Oxide
  • myrcene
  • Limonene
  • caryophyllene
  • Nitric Oxide Synthase Type II
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1