β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

Biomolecules. 2019 Jul 31;9(8):326. doi: 10.3390/biom9080326.

Abstract

β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.

Keywords: CAIA; CB2 receptors; PPAR-γ; arthritis; β-caryophyllene.

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic / drug effects
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • NF-kappa B / metabolism
  • PPAR gamma / metabolism*
  • Polycyclic Sesquiterpenes / pharmacology*
  • Polycyclic Sesquiterpenes / therapeutic use
  • Receptor, Cannabinoid, CB2 / metabolism*

Substances

  • Cytokines
  • NF-kappa B
  • PPAR gamma
  • Polycyclic Sesquiterpenes
  • Receptor, Cannabinoid, CB2
  • caryophyllene
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9