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

by Selleckchem | Mar 10 2023

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.

Comments：

Summary:

The study aimed to explore the mechanism of kaempferol in treating asthma. The study found that kaempferol can bind to nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and inhibit NOX4-mediated autophagy, which is involved in the development of asthma. Kaempferol treatment decreased NOX4 expression, as well as the secretion of IL-25 and IL-33 in human bronchial epithelial cells induced by transforming growth factor (TGF)-β1. In ovalbumin (OVA)-challenged mice, kaempferol treatment improved airway inflammation and remodeling by suppressing NOX4-mediated autophagy. The study suggests that kaempferol may provide an effective therapeutic strategy for treating asthma.

Key findings:

Kaempferol can bind to NOX4 with good binding affinity.
Kaempferol treatment decreased NOX4 expression and NOX4-mediated autophagy in TGF-β1-induced human bronchial epithelial cells.
Kaempferol treatment decreased the secretion of IL-25 and IL-33 in TGF-β1-induced human bronchial epithelial cells.
Kaempferol treatment improved airway inflammation and remodeling in OVA-induced mice by suppressing NOX4-mediated autophagy.
The therapeutic effects of kaempferol were hampered by rapamycin treatment, which confirms the role of NOX4-mediated autophagy in asthma.
Significance:

This study provides new insights into the mechanism of kaempferol in treating asthma. By inhibiting NOX4-mediated autophagy, kaempferol may have therapeutic potential in treating asthma. The study also highlights the importance of NOX4-mediated autophagy in the pathogenesis of asthma, which may open new avenues for developing effective therapeutic strategies.