Navegando por Palavras-chave "Antiasthmatic"

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    Avaliação do efeito do Deidrodieugenol extraído das folhas de Nectandra leucantha (Lauraceae) em modelo experimental de asma grave
    (Universidade Federal de São Paulo (UNIFESP), 2020-04-17) Ponci, Vitor [UNIFESP]; Lago, João Henrique Ghilardi [UNIFESP]; Universidade Federal de São Paulo
    Asthma is a chronic disease with high global prevalence, affecting around 235 million people around the globe. In Brazil, a 10% prevalence is estimated, with approximately 2.500 deaths per year, according to DATASUS national database. Asthma control is based on corticosteroid therapy, however portions of asthmatic patients do not respond well to this treatment, originating the difficult-to-control severe asthma phenotype. These patients have elevated airway hyperresponsiveness, higher frequency of exacerbations and remodeling and are responsible for a significant portion of total healthcare costs with asthma due to hospitalizations, specially the mixed-granulocytic endotype. For this endotype of asthma, there is a significant contribution of neutrophils, besides the elevated concentration of eosinophils as well and no specific therapy available. The aim of this study was to isolate, from the leaves of Nectandra leucantha, the neolignoid dehydrodieugenol, which structure was defined through nuclear magnetic resonance and mass spectra analysis, allied with the validation of a synthetic approach for the acquisition of dehydrodieugenol from eugenol as starting material to evaluate its antiasthmatic potential in a mice model of mixed-granulocytic asthma. Dehydrodieugenol was administered intraperitoneally in three different regimen doses (10 mg/kg for 8 days, 10 mg/kg for 4 days and 20 mg/kg for 4 days) in ovalbumin-sensitized BALB/C male mice in order to find the most efficacious dose regimen to further evaluate its potential regarding improvement in lung function and inflammatory parameters in comparison to positive control dexamethasone (5 mg.kg-1, i.p.). Based on dose-response analysis, dehydrodieugenol (20 mg.kg–1) for 4 days of treatment was the only dose regimen that resulted in significant reduction on both eosinophils (ΔBISxOVA=6,09.104/mL; P<0,05) and neutrophils (ΔBISxOVA=2,40.104/mL; P<0,001) on bronchoalveolar lavage fluid in ovalbuminsensitized mice with no statistically difference from dexamethasone (P>0,05). As for lung function parameters, dehydrodieugenol (20 mg.kg–1) significantly reduced airway (ΔRawBISxOVA = 1,67 cmH2O.s/mL, P<0,05) and tissue (ΔGtis BISxOVA = 4,60 cmH2O.s/mL; P<0,05) resistance in comparison to ovalbumin group, with similar efficacy to positive control dexamethasone. Airway hyperresponsiveness to intravenous methacholine was reduced with dehydrodieugenol but was inferior to dexamethasone in higher doses. No changes were observed on elastance in any group. Dehydrodieugenol showed good overall safety profile, without any deaths or concerns observed during the protocol and no change in liver, thymus or spleen mass compared to saline control group. Moreover, its production has low costs and few steps, making it possible to produce in larger scales. Thus, dehydrodieugenol (20 mg.kg–1) showed great antiasthmatic potential for the treatment of mixed-granulocytic asthma, for the substitution or combination therapy with corticosteroids, in order to reduce the risk of adverse events related to its chronic use, and can be obtained in few steps through the chemical preparation from eugenol.