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Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation.

AbstractBACKGROUND AND PURPOSE:
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.
EXPERIMENTAL APPROACH:
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.
KEY 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 AND IMPLICATIONS:
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.
AuthorsAlexandre P Rogerio, Edinéia L Andrade, Daniela F P Leite, Cláudia P Figueiredo, João B Calixto
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 158 Issue 4 Pg. 1074-87 (Oct 2009) ISSN: 1476-5381 [Electronic] England
PMID19438512 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aerosols
  • Anti-Inflammatory Agents
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Interleukin-5
  • Monocyclic Sesquiterpenes
  • NF-kappa B
  • Sesquiterpenes
  • Transcription Factor AP-1
  • Leukotriene B4
  • humulene
  • Interferon-gamma
  • Ovalbumin
Topics
  • Administration, Oral
  • Aerosols
  • Animals
  • Anti-Inflammatory Agents (administration & dosage, pharmacology, therapeutic use)
  • Bronchoalveolar Lavage Fluid (chemistry, immunology)
  • Chemokine CCL11 (analysis)
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Eosinophils (drug effects)
  • Female
  • Immunohistochemistry
  • Interferon-gamma (analysis)
  • Interleukin-5 (analysis)
  • Leukotriene B4 (analysis)
  • Lung (drug effects, metabolism, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Monocyclic Sesquiterpenes
  • Monocytes (drug effects)
  • NF-kappa B (analysis, metabolism)
  • Neutrophils (drug effects)
  • Ovalbumin (administration & dosage, immunology)
  • Respiratory Hypersensitivity (drug therapy, pathology)
  • Sesquiterpenes (administration & dosage, pharmacology, therapeutic use)
  • Transcription Factor AP-1 (analysis, metabolism)

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