Inhaled braylin regulates Th2 response and induces relaxant effects in the airway muscles in a model of ovalbumin-induced asthma

Abstract

BackgroundCoumarins are compounds with wide and relevant pharmacological properties, being considered one of the most important chemical classes among natural compounds. Braylin (6-methoxyseselin) is a coumarin whose pharmacological properties have not yet been extensively explored. Previous studies have shown its anti-inflammatory and immunomodulatory activities, potentially associated with glucocorticoid receptors, plus it is a phosphodiesterase 4 inhibitor. Thus, the present study was designed to investigate the pharmacological potential of braylin for asthma treatment. MethodsMice induced to an asthma model using ovalbumin (OVA) were treated with vehicle, braylin, or dexamethasone via intraperitoneal injection or inhalation, and the bronchoalveolar lavage (BAL) was collected to evaluate infiltration of inflammatory cells, and cytokine levels. Histopathological and morphometric analysis of lung tissue were also conducted, while ex vivo isometric measurement assessed the effect of braylin on tracheal relaxation. ResultsBraylin (50 mg/kg) showed similar efficacy in reducing the total count of inflammatory cells in the BAL of asthmatic mice by inhalation or intraperitoneal route. Inhaled braylin reduced, in a dose-dependent manner (25 to 100 mg/kg), the total count of inflammatory cells in the BAL of OVA-induced mice, more specifically eosinophils and neutrophils. Plus, inhaled braylin reduced the BAL levels of IL-4, IL-5, and IL-13, cytokines involved in asthma Th2 response. It also reduced pulmonary inflammatory infiltrate and the occurrence of goblet cell metaplasia. In a set of ex vivo assays, braylin was able to induce concentration-dependent relaxation of the trachea from mice with or without OVA-induced asthma. ConclusionsThe present results suggest that braylin may be a promising candidate for the treatment of asthma by regulating the Th2 response, inducing relaxant effects in the airway muscles, and presenting efficacy by inhalation route.