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.
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Centro de Ciências Biológicas, Florianópolis, SC, Brazil.
Alexandre P
AP
Rogerio
Edinéia L
EL
Andrade
Daniela F P
DF
Leite
Cláudia P
CP
Figueiredo
João B
JB
Calixto
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