The Protective Effect of Astragalus Polysaccharides Against Cisplatin‑Induced Pulmonary Epithelial Cell Injury: An Integrated Network Toxicology and In Vitro Validation.

Cisplatin (CDDP) is a widely used anticancer drug that generates significant oxidative stress, resulting in lung inflammation and injury. Currently, there is limited research on the related mechanisms and strategies. Astragalus polysaccharides (APS) are the main bioactive molecules in Astragalus that possess immunomodulatory, anti-inflammatory and antioxidant activities, and are clinically used for preventing pulmonary fibrosis and treating lung inflammation. Therefore, the present study aimed to investigate the protective effects of APS on CDDP-induced lung epithelial cell injury using network toxicology and network pharmacology to predict the key pathways involved in CDDP-induced injury and APS-mediated protection, and validating the predictions using in vitro assays. Our results demonstrated that APS could significantly reduce the death rate of Beas-2B cells and attenuated the oxidative stress caused by CDDP. The mitochondrial function was enhanced, mitochondrial reactive oxygen species (ROS) was suppressed, malondialdehyde (MDA) content and ferrous iron were decreased, thereby inhibiting ferroptosis and alleviating lung cell injury induced by CDDP. Therefore, the present study demonstrated that APS may attenuate CDDP-induced oxidative stress and iron overload, thereby inhibiting ferroptosis and alleviating lung cell injury. The findings of the present study may provide a potential clinical application.