Efeito anti-inflamatório do Triterpeno Uvaol em modelos de inflamação alérgica em camundongos

Abstract

Allergic diseases affect millions of people and their prevalence has constantly increased in the world every decade. Among the clinical manifestations, the allergic asthma is considered a major public healthy problem due to its number of cases and death records. Currently, these diseases are treated either with glucocorticoids, anti-histamines, mast cell stabilizers or immunomodulators. Although these drugs exert a strong anti-allergic effects, the long-term use may lead to harmful side-effects. Thus, considering the increase of allergic manifestations in the population and the requirement for new therapeutic tools with less side-effects, the discovery of drug of natural origin have been gaining prominence. Among products from natural origin, triterpenes are secondary metabolites and represent the largest group of phytochemicals in many plant species. Pharmaceutical preparations containing this metabolites are used in several countries because of their medicinal properties, which include anti-inflammatory, analgesic, antipyretic, hepatoprotective, cardiotonic effects, among others. Taking into account these information, the aim of this study was to investigate uvaol anti-allergic efficacy in experimental mouse models of allergy triggered by ovalbumin in mice. Firstly, it was found that in a model of the paw edema induced by OVA and histamine, the oral pretreatment with uvaol 1 hour prior to stimulation reduced both edema. Then, using the same treatment protocol, it was found that in the allergic pleurisy model, using a single allergic challenge, the uvaol significantly inhibited leukocyte recruitment, specially eosinophils, 24 h after allergic stimulation. Furthermore, IL-5 also presented a decreased levels in the pleural fluid. Using murine asthma models, with three exposures to the antigen daily for three consecutive days, it was found that oral administration of uvaol 1 h before each allergic stimulation reduced the accumulation of total leukocytes, mainly eosinophils present in the pulmonary parenchyma as well as IL-5 levels present in the inflamed lung tissue. Moreover, was observed that pretreatment with uvaol reduced the production of mucus after stimulus in airways of asthmatic animals. Bronchoalveolar lavage (BAL) of asthmatics animals pretreated with uvaol were evaluated and it was detected a significantly reduction in total cell number and eosinophils, as well as significantly reduced levels of IL-5. However, the pretreatment with uvaol was not able to interfere with the production of reactive oxygen species (ROS) in cells of the bronchoalveolar lavage. Therefore, considering all the data obtained so far, it was demonstrated for the first time that uvaol has a treatment potential of allergic disorders by reducing leukocyte recruitment and IL-5 levels, but not interfering in the generation of reactive oxygen species. Thus, uvaol shows up as a potential therapeutic tool for the treatment of allergic inflammation. Further studies are necessary to understand its molecular mechanism of action.