Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw

Br J Pharmacol. 2007 Jul;151(5):618-27. doi: 10.1038/sj.bjp.0707270. Epub 2007 Apr 30.


Background and purpose: alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS.

Experimental approach: The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors.

Key results: Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK.

Conclusions and implications: Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal*
  • Blotting, Western
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cordia / chemistry*
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Edema / chemically induced*
  • Edema / pathology
  • Edema / prevention & control*
  • Electrophoretic Mobility Shift Assay
  • Foot / pathology
  • Interleukin-1beta / biosynthesis
  • Lipopolysaccharides*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Oils, Volatile / pharmacology*
  • Peroxidase / metabolism
  • Polycyclic Sesquiterpenes
  • Rats
  • Rats, Wistar
  • Receptor, Bradykinin B1 / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation / drug effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Oils, Volatile
  • Polycyclic Sesquiterpenes
  • Receptor, Bradykinin B1
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • caryophyllene
  • Peroxidase
  • Mitogen-Activated Protein Kinases