Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation.
OBJECTIVE
alpha-Humulene and trans-caryophyllene are plant sesquiterpenes with pronounced anti-inflammatory properties. Here, we evaluated the effects of these compounds in an experimental model of airways allergic inflammation.


METHODS
Female BALB/c mice, sensitized to and challenged with ovalbumin received daily alpha-humulene or trans-caryophyllene (50 mg.kg(-1), orally) or alpha-humulene (1 mg.mL(-1), by aerosol) as either a preventive (for 22 days) or therapeutic (from the 18th to the 22nd day) treatment. Dexamethasone or budesonide was used as a positive control drug. Inflammation was determined on day 22 post-immunization by leukocyte recruitment, interleukin-5 (IL-5), CCL11, interferon-gamma (IFN-gamma) and leukotriene (LT)B(4) levels in bronchoalveolar lavage fluid (BALF). In addition, transcription factors [nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1)] and P-selectin in lung tissue were measured by immunohistochemistry and mucus secretion by histochemistry.


RESULTS
Preventive or therapeutic treatments with alpha-humulene, but not with trans-caryophyllene, significantly reduced the eosinophil recruitment to the BALF. In addition, alpha-humulene recovery INF-gamma and reduced the IL-5, CCL11 and LTB(4) levels in BALF, as well as the IL-5 production in mediastinal lymph nodes (in vitro assay). Furthermore, alpha-humulene decreased the NF-kB and the AP-1 activation, the expression of P-selectin and the increased mucus secretion in the lung.


CONCLUSIONS
alpha-Humulene, given either orally or by aerosol, exhibited marked anti-inflammatory properties in a murine model of airways allergic inflammation, an effect that seemed to be mediated via reduction of inflammatory mediators, adhesion molecule expression and transcription factors activation.
Rogerio
Alexandre P
AP
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Centro de Ciências Biológicas, Florianópolis, SC, Brazil.
Andrade
Edinéia L
EL
Leite
Daniela F P
DF
Figueiredo
Cláudia P
CP
Calixto
João B
JB
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D054413:Chemokine CCL11 / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D007975:Leukotriene B4 / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D000081222:Monocyclic Sesquiterpenes; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000378:metabolism
D000336:Aerosols; D000893:Anti-Inflammatory Agents; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D015848:Interleukin-5; D000081222:Monocyclic Sesquiterpenes; D016328:NF-kappa B; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; D007975:Leukotriene B4; C042686:humulene; D007371:Interferon-gamma; D010047:Ovalbumin