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A5802 - Sakuranetin (5,4’-Dihydroxy-7-Methoxyflavanone) Reduces Airway Eosinophilic Inflammation in a Murine Model of Allergic Asthma Due to Different Mechanisms
Author Block: F. Roncon1, R. Silva1, C. R. Olivo2, F. Arantes-costa3, S. Grecco4, L. Caperuto5, I. Tiberio3, J. Lago6, C. M. Prado7; 1Bioscience, Federal University of São Paulo, Sao Paulo, Brazil, 2University of Sao Paulo, São Paulo, Brazil, 3Medicine, University of Sao Paulo, Sao Paulo, Brazil, 4Biological Science, Federal University of São Paulo, Sao Paulo, Brazil, 5Biological Science, Federal University of São Paulo, Diadema, Brazil, 6Federal University of ABC, Sao Bernardo, Brazil, 7Bioscience, Federal University of São Paulo, Santos, Brazil.
Rationale: Previous studies had shown that sakuranetin, a flavonoid derived from Baccharis retusa (Asteraceae), is involved in the control of eosinophilic inflammation in an experimental murine model of asthma. Flavonoids present anti-inflammatory and anti-oxidant properties, however the mechanisms involved in the anti-inflammatory effects remained unknown. STAT3-SOCS3 and MAPKinase pathways seem to be activated in chronic asthma. Considering the clinical relevance in understanding the mechanisms of this compound, our hypothesis is that sakuranetin treatment, reduced airway inflammation by modulation STAT3/SOCS3, MAPKinase or cholinergic anti-inflammatory pathways in a murine model of allergic chronic airway inflammation in BALB/C mice. Aim: To investigate the mechanisms involved in anti-inflammatory effects of sakuranetin in a model of allergic chronic airway inflammation. Methods: BALB/c mice previously sensitized to ovalbumin (OVA) (29 day protocol) received sakuranetin (20mg/Kg, OVA+SK) or vehicle (OVA+Ve) beginning on the 22nd day until the end of the OVA protocol. Saline was given to control animals and dexamethasone (OVA+DX) was given to ovalbumin as a positive control. Eosinophils were detected in bronchiolar alveolar lavage fluid (BALF), cytokines in lung homogenate and IgE levels in serum. Immunoblotting was performed to detect the levels of JAK2, total and phosphorylated STAT3, SOCS3, total and phosphorylated ERK1/2, p38 and VAChT (vesicular acetylcholine transporter) in lung. Results: Eosinophils in BALF, Th2 (IL-13, IL-4 and RANTES) and Th17 (IL-17) cytokines in lung and IgE in serum were increased in OVA+Ve group. In addition, OVA+Ve group showed increased phosphorylation of STAT3, SOCS3, phosphorylation of p38 and ERK 1/2 as well as increased levels of VAChT protein in the lung. The SK treatment reduced eosinophils, IgE levels, Th2 and Th17 cytokines in OVA+SK group in the same levels of data obtained in OVA+DX-treated group. Moreover, SK treatment reduced the phosphorylation of STAT3, p38 and ERK 1/2 in lung, without interfere with the levels of SOCS3 and VAChT in lung of OVA-sensitized animals. Conclusions: The STAT3 and MAPKinase pathways are involved in the anti-inflammatory effects of sakuranetin in an experimental model of allergic airway inflammation. These data reinforce previous reports that sakuranetin is an important compound to be considered in asthma elucidating some of the mechanisms involved in these responses.