Efeito do extrato aquoso das folhas de Echinodorus grandiflorus, de suas frações metanólica e residual e do ácido ferúlico na modulação da resposta imune no modelo de alergia pulmonar induzida por ova

Abstract

Asthma is a heterogeneous disease characterized by chronic airway inflammation, defined by history of respiratory symptoms and associated with variable expiratory flow limitation. Regarded as a serious health problem affecting an estimated over 300 million people worldwide. The immune response in asthma is predominantly Th2 lymphocytes, with high levels of total and allergen-specific IgE and bronchial eosinophilia. Asthma treatment is aimed at controlling the disease and the drugs used currently have systemic side effects and generally are not effective in cases of asthma are difficult to control, and it is crucial the developing new treatments. Echinodorus grandiflorus is a plant species known as “chapéu-de-couro” widely used for their anti-inflammatory properties. In previous work, the treatment with the aqueous extract of this specie reduced the pathogenic Th2 response in the OVAinduced pulmonary allergy. The ferulic acid is a phenolic acid widely present in the plant kingdom and found in E. grandiflorus which has antioxidant and antiinflammatory activities. In this study, the effect of aqueous extract of E. grandiflorus, its methanol and residual fractions, and ferulic acid in modulating the immune response of pulmonary allergy model was investigated. The aqueous extract, fractions and ferulic acid were analyzed by high-performance liquid chromatography. For induction of pulmonary allergy female BALB/c mice were intraperitoneally sensitized with OVA and alum on days 0 and 14. On days 21, 23, 25, 27 and 29, animals were challenged with OVA 1% for 20 minutes. Treatments were administered by gavage, between days 21 and 29 of protocol. The serum, bronchoalveolar lavage fluid and lungs were collected. Chromatographic analysis revealed two phenolic acids as major components of extract and fractions that possibly are related to their pharmacological activities, however ferulic acid was not identified in the extract and fractions. The treatments were promising in the modulation of pathogenic Th2 response, with the best results obtained with the aqueous extract 25 mg/kg, methanolic fraction 25 mg/kg, residual fraction 100 mg/kg and ferulic acid 25 mg/kg. The treatments reduced the inflammatory infiltration in lung tissue, the number of goblet cells in lung tissue, the number of total cells, eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage, the levels of TSLP, IL-25, IL33, IL-4, IL-5, IL-13, IFN-γ, CCL5, CCL11, and CCL20 in lung tissue, and the serum levels of IgE and IgG1. Taken together, these results indicate that the aqueous extract of E. grandiflorus, methanolic and residual fractions, and ferulic acid reduced the allergic pulmonary inflammation, act primarily in the early phase of the immune response, reducing the release of cytokines and chemokines by airways epithelial cells.