Polyphenol-rich Salsola imbericata extract attenuates experimental lung injury via modulating oxidative stress, NLRP3 inflammasome activation and apoptosis singling.

Salsola imbericata is a halophytic plant with promising yet underexplored pharmacological potential. The present study aimed to characterize the metabolite profile of its ethanolic extract (SI-EtOH) and evaluate its protective effects against experimentally induced lung injury. UPLC-PDA-ESI-TOF-MS/MS-based metabolomics enabled the tentative identification of 62 metabolites belonging to diverse classes, including phenolic acids and their glycosides, flavonoids (notably isorhamnetin derivatives), alkaloids, triterpenoid saponins, fatty acid amides, and organic acids. Pulmonary injury induction resulted in marked oxidative stress, evidenced by a significant increase in malondialdehyde (MDA) levels by 463.3% and a depletion of glutathione (GSH) by 94.2% compared to the control group. Treatment with SI-EtOH (200 and 400 mg/kg) significantly reduced MDA levels by 148.4% and 348.3%, respectively, and restored GSH levels by 26% and 59.8%. Inflammation was also significantly attenuated, with reductions in IL-1B by 148.4% and 348.3%, and IL-18 by 15.8% and 41.5% at the two dose levels, respectively. Furthermore, SI-EtOH suppressed NLRP3 inflammasome activation by 25.0% and 82.1%, and decreased caspase-1 levels by 38.2% and 89.2%, indicating a pronounced anti-inflammatory and anti-apoptotic effect. Histopathological and immunohistochemical findings supported these results, demonstrating improved lung architecture, reduced inflammatory infiltration, and decreased cleaved caspase-3 expression. Overall, S. imbericata exhibits potent protective effects against lung injury, likely mediated through its antioxidant, anti-inflammatory, and anti-apoptotic activities, supporting its potential as a therapeutic candidate for pulmonary disorders.