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

Background and purpose: α‐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 α‐humulene and trans‐caryophyllene on the acute inflammatory responses elicited by LPS. Experimental approach: The biological activities of α‐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‐κB and up‐regulated expression of kinin B1 receptors. Key results: Treatment with either α‐humulene or trans‐caryophyllene effectively reduced neutrophil migration and activation of NF‐κB induced by LPS in the rat paw. However, only α‐humulene significantly reduced the increase in TNF‐α and IL‐1β levels, paw oedema and the up‐regulation of B1 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 α‐humulene and trans‐caryophyllene inhibit the LPS‐induced NF‐κB activation and neutrophil migration, although only α‐humulene had the ability to prevent the production of pro‐inflammatory cytokines TNF‐α and IL‐1β and the in vivo up‐regulation of kinin B1 receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes α‐humulene and trans‐caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases. British Journal of Pharmacology (2007) 151, 618–627; doi:10.1038/sj.bjp.0707270