Kaempferol inhibits airway inflammation induced by allergic asthma through NOX4-Mediated autophagy

Kaempferol has important medicinal value in the treatment of asthma. However, its mechanism of action has not been fully understood and needs to be explored and studied.A binding activity of kaempferol with nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) was analyzed by molecular docking. Human bronchial epithelial cells (BEAS-2B) were treated with different concentrations (0, 1, 5, 10, 20, 40 μg/mL) of kaempferol to select its suitable concentration. In the transforming growth factor (TGF)-β1-induced BEAS-2B, cells were treated with 20 μg/mL kaempferol or 20 μM GLX35132 (a NOX4 inhibitor) to analyze its effects on NOX4-mediated autophagy. In the ovalbumin (OVA)-induced mice, 20 mg/kg kaempferol or 3.8 mg/kg GLX351322 administration was performed to analyze the therapeutic effects of kaempferol on NOX4-mediated autophagy. An autophagy activator, rapamycin, was used to confirm the mechanism of kaempferol in treatment of allergic asthma.A good binding of kaempferol to NOX4 (score = -9.2 kcal/mol) was found. In the TGF-β1-induced BEAS-2B, the NOX4 expression was decreased with kaempferol dose increase. The secretions of IL-25 and IL-33, and the NOX4-mediated autophagy were significantly decreased by kaempferol treatment in the TGF-β1-induced BEAS-2B. In the OVA-challenged mice, kaempferol treatment improved airway inflammation and remodeling through suppressing NOX4-mediated autophagy. The rapamycin treatment clearly hampered the therapeutic effects of kaempferol in the TGF-β1-induced cells and OVA-induced mice.This study identifies kaempferol binds NOX4 to perform its functions in the treatment of allergic asthma, providing an effective therapeutic strategy in the further treatment of asthma.