ABSTRACT
Carvone is a monoterpene found in nature in the form of enantiomers (S- and R-). While previous research has demonstrated the anti-inflammatory and anti-allergic effects of carvone, the influence of carvone enantiomeric composition on its anti-allergic activity remains to be investigated. This study aimed to evaluate the anti-allergic activity of carvone enantiomers in a murine model of airway allergic inflammation induced by sensitization and challenge with ovalbumin (OVA). The oral treatment with R-carvone or S-carvone 1 h before each challenge inhibited the number of leukocytes and eosinophils in the bronchoalveolar lavage (BAL). R-carvone inhibited leukocyte infiltration and mucus production in the lung, which was correlated with decreased production of OVA-specific IgE in the serum and increased concentrations of IL-10 in the BAL. On the other hand, the administration of S-carvone had little inhibitory effect on inflammatory infiltration and mucus production in the lung, which might be associated with increased production of IFN-γ in the BAL. When administered 1 h before each sensitization, both enantiomers inhibited eosinophil recruitment to the BAL but failed in decreasing the titers of IgE in the serum of allergic mice. Our data indicate that carvone enantiomers differentially modulated IgE-mediated airway inflammation in mice. In conclusion, unlike S-carvone, R-carvone has the potential to be used in anti-allergic drug development.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cyclohexane Monoterpenes/pharmacology , Immunoglobulin E/immunology , Immunomodulation/drug effects , Inflammation/immunology , Respiratory Tract Diseases/immunology , Animals , Anti-Inflammatory Agents/chemistry , Chemotaxis/drug effects , Chemotaxis/immunology , Cyclohexane Monoterpenes/chemistry , Cytokines/biosynthesis , Disease Models, Animal , Eosinophils/drug effects , Eosinophils/immunology , Eosinophils/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung/pathology , Mice , Respiratory Tract Diseases/drug therapy , Respiratory Tract Diseases/metabolism , Respiratory Tract Diseases/pathology , Severity of Illness IndexABSTRACT
The alkaloid 2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)phenol (MHTP) was synthesized to prospect new compounds with therapeutic properties. Thus, the goal of this study was to evaluate the MHTP anti-inflammatory effect by in vivo and in vitro assays. The MHTP toxicity was analyzed. We found that MHTP pre-treatment (2.5-10 mg/kg) showed antiedematogenic effect (p < 0.05) in carrageenan-induced paw edema by inhibiting the PGE2 action independently of mast cell degranulation or histamine activity. MHTP also diminished (p < 0.01) total leukocyte migration in 41.5% into peritoneal cavity during carrageenan-induced peritonitis, reducing polymorphonuclear cells (PMNs) (59.6%) and proteins levels (29.4%). MHTP in an experimental model of acute lung injury inhibited (p < 0.001) total inflammatory cell migration into the lungs and PMNs in 58% and 67.5%, respectively. Additionally, MHTP did not present cytotoxicity at concentrations of 10, 25 or 50 µM but decreased (p < 0.001) the NO production in 24%, 47% and 39%, respectively. The alkaloid also reduced (p < 0.001, in lipopolysaccharide (LPS)-stimulated macrophages (1 µg/mL), IL-1ß, IL-6 and IL-10 levels in 35.7%, 31.0% and 33.4%, respectively. The results obtained in this study allow us to conclude that the inedited synthetic alkaloid, MHTP has anti-inflammatory effect by inhibiting PGE2 function as well as inhibiting inflammatory cell migration to the inflamed site and attenuated the acute lung injury disease by inhibiting the migration of neutrophil to the lung. However, further studies will be carried out to demonstrate the mechanisms of action of the molecule and explore its potential as a future drug to treat inflammatory processes.
