Astaxanthin suppress ferroptosis through the Akt1-FoxO3a signaling pathway to alleviates brain injury after intracerebral hemorrhage.

Intracerebral hemorrhage is the second most common subtype of stroke, characterized by high mortality and disability rates. To date, the mechanism of brain injury caused by intracerebral hemorrhage remains unclear, and there are no effective treatments to delay the progression of brain injury after intracerebral hemorrhage. Increasing evidence suggests that oxidative stress plays a crucial role in secondary injury induced by intracerebral hemorrhage, and ferroptosis plays a dominant role in the pathogenesis of brain injury after intracerebral hemorrhage. In this study, we demonstrated in an in vitro hemin-induced PC12 cell model that astaxanthin improved cell viability, inhibited oxidative stress after intracerebral hemorrhage, and suppressed ferroptosis by upregulating the expression of glutathione peroxidase 4 and solute carrier family 7a member 11. In an in vivo autologous blood injection intracerebral hemorrhage rat model, we confirmed that astaxanthin could resist oxidative stress, ferroptosis, and further inflammatory responses by upregulating the expression of glutathione peroxidase 4 and solute carrier family 7a member 11 through the Akt1-FoxO3a pathway to protect against brain injury after intracerebral hemorrhage.