Protective effects and mechanism of action of ruscogenin in a mouse model of ovalbumin-induced asthma

Ruscogenin is a natural product exhibiting anti-inflammatory, antioxidant, and anti-apoptotic effects; however, its effectiveness for asthma management has not yet been reported. The aim of this study was to explore the role of ruscogenin in airway inflammation and apoptosis in asthma.In vivo, female 6- to 8-week-old CL57 mice were sensitized to ovalbumin and challenged intranasally for 7 days. One group was gavaged with ruscogenin before ovalbumin challenge. At the end of the challenge period, airway hyperresponsiveness and airway inflammation were evaluated. Enzyme-linked immunosorbent assay was used to estimate the oxidative stress levels. A terminal deoxynucleotidyl transferase dUDP nick-end labeling assay was used to determine the extent of apoptosis. Immunohistochemistry and western blotting were performed to examine VDAC1 expression. In vitro, human bronchial epithelial (HBE) cells were treated with H2O2, ruscogenin, or disulfonate salt, and flow cytometry was used to calculate the apoptosis ratio and detect mitochondrial calcium levels.In vivo, ruscogenin improved airway hyperresponsiveness and airway inflammation, while reducing oxidative stress, the apoptosis ratio and VDAC1 expression in asthmatic lungs. In vitro, ruscogenin attenuated apoptosis in HBE cells by decreasing the levels of VDAC1 expression and mitochondrial calcium.Ruscogenin reduced oxidative stress and apoptosis in the airway epithelium by inhibiting VDAC1 expression and mitochondrial handling of calcium.