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.

Abstract

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.

• Authors: R Medeiros, G F Passos, C E Vitor, J Koepp, T L Mazzuco, L F Pianowski, M M Campos, J B Calixto
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 151 Issue 5 Pg. 618-27 (Jul 2007) ISSN: 0007-1188 [Print] England
• PMID: 17471174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal
• Blotting, Western
• Cell Nucleus (drug effects, metabolism)
• Cordia (chemistry)
• Cytosol (drug effects, metabolism)
• Edema (chemically induced, pathology, 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, 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)