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

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

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1
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Centro de Ciências Biológicas, Florianópolis, SC, Brazil.

Abstract

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 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.

PMID:
19438512
PMCID:
PMC2785529
DOI:
10.1111/j.1476-5381.2009.00177.x
[Indexed for MEDLINE]
Free PMC Article
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