NOTCH pathway was involved in Kaempferol 3-O-gentiobioside attenuated airway inflammation and mucus hypersecretion.

Allergic asthma is an inflammatory condition characterized by the release of pro-inflammatory cytokines and the expansion of mucus-producing cells. This research aimed to evaluate the impact of Kaempferol 3-O-gentiobioside (K3G), extracted from Sauropus spatulifolius Beille leaves, on inflammatory cytokine secretion and mucus overproduction in IL-13-stimulated airway epithelial cells (16HBE cells) and ovalbumin (OVA)-induced allergic asthma mouse models. Studies have found that K3G significantly reduces the release of pro-inflammatory cytokines (IgE, TNF-α, histamine, IL-1β, IL-6, and IL-8) induced by IL-13. It also mitigating the expression of the mucin5AC (MUC5AC). Additionally, K3G also downregulated the expression of NLRP3, TLR4, p-IκBα, and p-P65 proteins. In an OVA-induced mouse asthma model, K3G treatment reduced the secretion of pro-inflammatory cytokines, and inhibited the increase in mucus-secreting cells in a dose-dependent manner. Furthermore, exposure to IL-13 and OVA increased the expression of NOTCH signaling receptors in both 16HBE cells and lung tissues of the mice. K3G treatment effectively targeted NOTCH1 and inhibits activation of the NOTCH pathway. In conclusion, K3G alleviates asthma-related airway alterations by suppressing inflammatory cytokines and excessive mucus secretion via the NOTCH signaling pathway. These results indicate the therapeutic promise of K3G in treating allergic asthma.