ABSTRACT
Croton rhamnifolioides is used in popular medicine for the treatment of inflammatory diseases. The objective of this study was to characterize and evaluate the anti-inflammatory effect of C. rhamnifolioides essential oil complexed in ß-cyclodextrin (COEFC). The physicochemical characterization of the complexes was performed using different physical methods. The anti-inflammatory activity was evaluated in vivo by ear edema, paw edema, cotton pellet-induced granuloma, and vascular permeability by Evans blue extravasation. The mechanism of action was validated by molecular docking of the major constituent into the cyclooxygenase-2 (COX-2 enzyme). All doses of the COEFC reduced acute paw edema induced by carrageenan and dextran, as well as vascular permeability. Our results suggest the lowest effective dose of all samples inhibited the response induced by histamine or arachidonic acid as well as the granuloma formation. The complexation process showed that the pharmacological effects were maintained, however, showing similar results using much lower doses. The results demonstrated an involvement of the inhibition of pathways dependent on eicosanoids and histamine. Complexation of ß-cyclodextrin/Essential oil (ß-CD/EO) may present an important tool in the study of new compounds for the development of anti-inflammatory drugs.
ABSTRACT
Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a ß-cyclodextrin-isopulegol inclusion complex (ISO/ß-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/ß-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/ß-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1ß and TNF-α. ISO and ISO/ß-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in ß-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.
ABSTRACT
The species Croton rhamnifolioides, belonging to the Croton genus, is known in ethnomedicine as "quebra faca" and is used in the treatment of stomach pain, vomiting and fever. This study aims to evaluate the anti-edematogenic and anti-inflammatory effect of Croton rhamnifolioides leaf essential oil (OEFC) and its major constituent: 1,8-cineole (eucalyptol). The essential oil was extracted from fresh leaves through a hydrodistillation system. The chemical analysis was determined by gas chromatography-mass spectrometry (GC-MS). The acute anti-inflammatory activity was determined from the models of: ear edema by the single application of croton oil, paw edema induced by: carrageenan, dextran, histamine and arachidonic acid, while vascular permeability was determined by Evans blue extravasation and chronic anti-inflammatory activity by granuloma induction using the implantation of cotton pellets. The GC-MS results identified and quantified 11 constituents, with the major component being 1,8-cineole (41.33%). The OEFC (20mg/mL) and 1,8-cineole (8.26mg/mL) significantly reduced the edema induced by croton oil by 42.1 and 34.9%, respectively. The OEFC (25, 50, 100 and 200mg/kg) and 1,8-cineole (10.33, 20.66, 41.33 and 82.66mg/kg) statistically reduced paw edema induced by carrageenan, dextran as well as vascular permeability (protein extravasation). The OEFC (25mg/kg) and 1,8-cineole (10.33mg/kg) demonstrated efficacy in reducing edema induced by histamine and arachidonic acid and granuloma. In conclusion, the OEFC and 1,8-cineole have anti-inflammatory activity in the acute and chronic phase, suggesting therapeutic potential as a source for the development of new anti-inflammatory agents.
