Astragalus polysaccharide mitigates the airway inflammation in bronchial asthma by regulating Hedgehog/NLRP3/GSDMD pathway

Asthma is a significant allergic condition affecting the respiratory system. Numerous compounds extracted from traditional Chinese herbal medicine show potential benefits for treating airway inflammation associated with bronchial asthma. Astragalus polysaccharide (APS), a class of major extracts from Astragalus membranaceus, exhibit many anti-inflammatory effects. Nonetheless, the underlying mechanisms of APS in asthma remain to be clarified. This study aims to assess the effect and the mechanism by which APS against asthma. The ovalbumin (OVA)-induced asthma mice were employed to assess the roles of APS <i>in vivo</i>. Lung tissues were used for H&E, PAS, and Masson staining. Inflammatory cells in bronchoalveolar lavage fluid (BALF) and chemokines in both BALF and serum samples were determined by hemocytometer and ELISA. The expression of the Hedgehog/NLRP3/GSDMD pathway in lung tissues was measured by quantitative real-time PCR and Western blotting. APS displayed lung-protective effects through decreasing airway inflammation and airway remodeling in OVA-induced asthma mice, which was demonstrated by decreasing the number of inflammatory cells and the cytokine levels in BALF and serum, and histopathological changes in lung tissues. Besides, APS treatment could decrease the expression of SHH, SMO, Gli1, Ptch1, NLRP3, GSDMD-N, ASC, Cleaved caspase-1, IL-18, IL-1β, CARMA3, BCL10, and MALT1 in lung tissues. APS improves clinical symptoms of OVA-induced bronchial asthma. The anti-asthmatic effects of APS may be related to the regulatory influences of the Hedgehog/NLRP3/GSDMD pathway.