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

Br J Pharmacol. 2009 Oct;158(4):1074-87. doi: 10.1111/j.1476-5381.2009.00177.x. Epub 2009 May 8.


Background 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, 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aerosols
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / 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*
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Monocyclic Sesquiterpenes
  • Monocytes / drug effects
  • NF-kappa B / analysis
  • NF-kappa B / metabolism
  • Neutrophils / drug effects
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Respiratory Hypersensitivity / drug therapy*
  • Respiratory Hypersensitivity / pathology
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Transcription Factor AP-1 / analysis
  • Transcription Factor AP-1 / metabolism


  • 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