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.
OBJECTIVE
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.


METHODS
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.


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
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.
Medeiros
R
R
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Santa Catarina, Brazil.
Passos
G F
GF
Vitor
C E
CE
Koepp
J
J
Mazzuco
T L
TL
Pianowski
L F
LF
Campos
M M
MM
Calixto
J B
JB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D031213:Cordia / Q000737:chemistry*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004487:Edema / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D024202:Electrophoretic Mobility Shift Assay; D005528:Foot / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009822:Oils, Volatile / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D000081223:Polycyclic Sesquiterpenes; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009822:Oils, Volatile; D000081223:Polycyclic Sesquiterpenes; D043783:Receptor, Bradykinin B1; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C024714:caryophyllene; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases