Anti-inflammatory and anti-edematogenic action of the Croton campestris A. St.-Hil (Euphorbiaceae) essential oil and the compound β-caryophyllene in in vivo models

Abstract

BackgroundInflammation makes up a set of vascularized tissue reactions acting in the defense of the body against harmful stimuli. Natural products are a lower cost alternative with better benefit, often used in popular medicine in the treatment of inflammatory processes. Several species from the genus Croton have scientifically proven anti-inflammatory action. PurposeThis study aims to analyze the chemical composition of the Croton campestris A. St.-Hil essential oil (EOCC), derived from fresh leaves, as well as to evaluate the anti-inflammatory potential and the possible mechanisms of action of the EOCC and its constituent β-caryophyllene. MethodsThe assays were performed in in vivo models of acute and chronic inflammation. Initially, the chemical composition of the EOCC was determined and its oral toxicity was evaluated, followed by the evaluation of its topical antiedematogenic effect through acute and chronic ear edema induced by Croton oil. For the systemic verification of an anti-inflammatory action, the abdominal contortions, formalin test, paw edema induced by carrageenan, dextran, histamine and arachidonic acid models, as well as a peritonitis test, vascular permeability and granuloma assays were performed. ResultsThe evaluation of the essential oil chemical composition revealed the presence of β-caryophyllene (15.91%), 1,8-cineol (16.98%) and germacrene-D (14.51%) as its main constituents. The EOCC had no relevant clinical toxicity on oral administration, with an LD50 of more than 5000 mg/kg. The tested substances showed anti-inflammatory action in the abdominal contortions, paw edema induced by carrageenan, dextran, histamine and arachidonic acid models, the formalin test, peritonitis test and vascular permeability; however, β-caryophyllene had no significant effect on the granuloma assay. This suggests as a hypothesis that both substances tested showed significant influence on the arachidonic acid and histamine pathway reducing edema in these models. ConclusionThe tested substances have a clinically safe profile, additionally the EOCC and β-caryophyllene presented relevant anti-inflammatory activity. This study supports the hypothesis that β-caryophyllene, in association with other constituents present in the EOCC such as 1,8-cineole, contributed to the anti-inflammatory effect observed, in addition to suggesting that one of the mechanisms of action probably involves the inhibition of cytokines with the involvement of the arachidonic acid and histamine pathways.