Astragalus polysaccharide alleviates IL-13-induced oxidative stress injury in nasal epithelial cells by inhibiting WTAP-mediated FBXW7 m6A modification.

BACKGROUND: Allergic rhinitis (AR) a common and complicated upper airway disease mediated by specific IgE antibodies. Our study aims to explore the pharmacological effects of astragalus polysaccharide (APS) on AR and elucidate the mechanisms involved. METHODS: RT-qPCR and Western blotting were used to analyze mRNA and protein expression. Interleukin (IL)-13-treated human nasal epithelial cells (hNECs) was employed as the AR cell model. Cell apoptosis and viability were evaluated by TUNEL staining and MTT assay, respectively. ROS level was examined by the DCFH-DA probe. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels were measured by the corresponding kits. FBXW7 m6A modification level was assessed by MeRIP assay. METHODS: Our results showed that APS treatment reduced cell apoptosis, ROS, and MDA levels while increasing SOD, CAT, and GSH-Px levels in IL-13-treated hNECs by activating the Nrf2/HO-1 pathway. Moreover, APS alleviated IL-13-induced oxidative stress injury in hNECs by downregulating WTAP. In addition, WTAP knockdown increased FBXW7 mRNA stability by regulating FBXW7 mRNA m6A modification. It also turned out that APS alleviated IL-13-induced oxidative stress injury in hNECs through the WTAP/FBXW7 axis. CONCLUSIONS: Taken together, APS inhibited WTAP-mediated FBXW7 m6A modification to alleviate IL-13-induced oxidative stress injury in hNECs.