Ginsenoside Rb1 inhibits ferroptosis to ameliorate hypoxic-ischemic brain damage in neonatal rats

•The protective effects and potential mechanism of GsRb1 in hypoxic-ischemic brain injury.•GsRb1 could rescuse the activity of System Xc and the levels of antioxidant substances.•GsRb1 meanwhile inhibit the levels of lipid oxidation and inflammatory indexes.•GsRb1 inhibit ferroptosis through improving oxidative stress as well as inflammation. Hypoxic ischemic encephalopathy (HIE) is among the leading causes of neonatal mortality, and currently there is no effective treatment. Ginsenoside Rb1 (GsRb1) is one of the principal active components of ginseng, and has protective benefits against oxidative stress, inflammation, hypoxic injury, and so on. However, the role and underlying mechanism of GsRb1 on HIE are unclear. Here, we established the neonatal rat hypoxic-ischemic brain damage (HIBD) model in vivo and the PC12 cell oxygen-glucose deprivation (OGD) model in vitro to investigate the neuroprotective effects of GsRb1 on HIE, and illuminate the potential mechanism. Our results showed that GsRb1 and the ferroptosis inhibitor liproxstatin-1 (Lip-1) could significantly restore System Xc activity and antioxidant levels as well as inhibit lipid oxidation levels and inflammatory index levels of HIBD and OGD models. Taken together, GsRb1 might inhibit ferroptosis to exert neuroprotective effects on HIE through alleviating oxidative stress and inflammation, which will set the foundation for future research on ferroptosis by reducing hypoxic-ischemic brain injury and suggest that GsRb1 might be a promising therapeutic agent for HIE.