Related Experiment Video
Updated: May 10, 2026
Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Ginsenoside Rb1 attenuates hyperoxia-induced lung injury in neonatal rats by inhibiting ferroptosis via the system
Huidan Lian1, Haiyu Zhou2, Jie Dong3
1Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Background:
Hyperoxia-induced lung injury (HALI) is a common and severe complication in neonatal intensive care units, and there is currently no effective therapy available. Ferroptosis, a newly recognized form of iron-dependent regulated cell death, has recently been implicated in the pathogenesis of this disease. Ginsenosides are bioactive components extracted from ginseng. Among them, ginsenoside Rb1 (GsRb1) belongs to the protopanaxadiol-type saponins, and its molecular structure is C54H92O23. This study aimed to investigate the protective effects and underlying mechanisms of GsRb1 in neonatal rats with hyperoxia-induced lung injury.
Methods:
A neonatal rat model of hyperoxia-induced lung injury and an in vitro alveolar epithelial cell model of hyperoxic damage were established. Histopathological changes, inflammatory cytokines, oxidative stress, and key ferroptosis-related proteins like the solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression were assessed using hematoxylin-eosin staining, enzyme-linked immunosorbent assay, Western blotting, transmission electron microscopy, and immunofluorescence. The ferroptosis inhibitor, liproxstatin-1(Lip-1), and the system Xc- inhibitor, erastin, were used for mechanistic validation.
Results:
GsRb1 significantly alleviated hyperoxia-induced alveolar structural disruption, pulmonary edema, and elevated levels of inflammatory cytokines (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α(TNF-α)). Moreover, GsRb1 reversed the characteristic features of hyperoxia-induced ferroptosis, including decreased intracellular ferrous iron and malondialdehyde levels, improved mitochondrial morphology, and regulation of ferroptosis-associated proteins, i.e., upregulating SLC7A11, GPX4, and Ferritin heavy chain 1 (FTH1) while downregulating Transferrin receptor protein (TFR). The protective effects of GsRb1 were comparable to those of the classical ferroptosis inhibitor Lip-1. Molecular docking analysis revealed that GsRb1 could directly and stably bind to the active pocket of the SLC7A11. Furthermore, GsRb1 reversed erastin-induced pulmonary injury and ferroptosis, confirming that its protective effects depend on system Xc- pathway activation.
Conclusion:
GsRb1 exerts protective effects against hyperoxia-induced lung injury in neonatal rats by targeting SLC7A11 to activate the system Xc- pathway, thereby inhibiting ferroptosis in alveolar epithelial cells.
