Solasodine binds to glucocorticoid receptor to ameliorate airway remodeling and excessive autophagy in bronchial smooth muscle cells for allergic asthma

This study was designed to analyze the potential mechanism of action of solasodine by which solasodine suppresses airway remodeling and autophagy in allergic asthma. Human bronchial smooth muscle cells (HBSMCs) were induced by 10 ng/mL of transforming growth factor (TGF)-β1 for 24 h and treated with a series of solasodine (10, 20, 40 μM) for another 24 h. In the TGF-β1-induced HBSMCs, solasodine treatment downregulated the α- smooth muscle actin (α-SMA) level but upregulated the glucocorticoid receptor (GR) level compared with the vehicle treatment (P < 0.05). The binding of solasodine to GR was analyzed using molecular docking and MST measurement. As a result, a direct interaction between solasodine and GR was found. RU486, a GR antagonist, was used to verify that solasodine attenuates TGF-β1-induced fibrosis and autophagy by regulating GR. The RU486 treatment suppressed the effects of solasodine on the TGF-β1-induced FOXO3A, fibrosis and autophagy in the HBSMCs. Subsequently, C57BL/6 J mice were induced with ovalbumin (OVA) and treated with 10 mg/kg/d of solasodine or 2.5 mg/kg/d of dexamethasone (Dex). In the OVA-induced mice, solasodine or Dex treatment attenuated airway inflammation, airway remodeling, and abnormal autophagy compared with the vehicle treatment (P < 0.05). Moreover, the solasodine or Dex treatment increased the expression of GR and FOXO3A in the OVA-induced mice compared with the vehicle treatment (P < 0.01). This study showed that solasodine ameliorated airway remodeling and abnormal autophagy by binding to GR in the allergic model, presenting a possible therapeutic agent for the allergic asthma.