Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Kaempferol; NADPH oxidase 4; Th2 inflammation; autophagy.