Astragaloside IV Reduces Lung Epithelial Cell Pyroptosis via TXNIP-NLRP3-GSDMD pathway.

This study aimed to investigate the detrimental impact of cigarettes on lung cells and the potential effects of astragaloside IV on lung epithelial cell oxidative stress and pyroptosis. The research utilized cigarette smoke extract (CSE) to stimulate lung epithelial cells BEAS-2B, assessed cytotoxicity using the CCK-8 method, and measured changes in reactive oxygen species (ROS) and mitochondrial membrane potential with a probe method. Additionally, Seahorse XF24 was employed to analyze the impact of CSE on mitochondria in lung epithelial cells. Furthermore, LPS and cigarette combination-treated mice were created, alveolar damage was evaluated using HE staining, and changes in the key protein GSDMD of pyroptosis were detected using western blot (WB). The study also utilized the CCK-8 method to assess the potential toxic effects of astragaloside IV on lung epithelial cells, and the probe method to monitor changes in ROS and mitochondrial membrane potential. WB analysis was conducted to observe protein alterations in the TXNIP/NLRP3/GSDMD pathway. CSE concentration-dependently reduced cell activity, increased cellular ROS levels, and decreased mitochondrial membrane potential. CSE also decreases basal respiratory capacity, respiratory reserve capacity, and ATP production levels in cells. In LPS and cigarette combination-treated mice, cigarette smoke caused the alveolar septum to break and alveoli to enlarge, while increasing the expression of pyroptosis-related protein GSDMD. Astragaloside IV did not show significant cytotoxic effects within 48 h of treatment and could reduce CSE-induced ROS levels while increasing mitochondrial membrane potential. WB results indicated that astragaloside IV reduced the activation of the TXNIP/NLRP3/GSDMD signaling pathway in lung epithelial cells exposed to CSE. Our study demonstrates that CSE induces oxidative stress and impairs mitochondrial function in pulmonary epithelial cells, while astragaloside IV can potentially reverse these effects by inhibiting the TXNIP-NLRP3-GSDMD signaling pathway, thereby mitigating CSE-induced pulmonary disease and epithelial cell pyroptosis.