Baicalin Attenuates Ferroptosis after Subarachnoid Hemorrhage via the PI3K/AKT/GPX4 and NLRP3 Axis

Subarachnoid hemorrhage (SAH) is a common subtype of stroke characterized by bleeding into the subarachnoid space. Increasing evidence suggests that neuronal ferroptosis- an iron-dependent, non-apoptotic form of cell death-contributes significantly to the secondary brain injury and poor prognosis observed in SAH patients. However, there are currently no effective pharmacological interventions specifically targeting ferroptosis in this context.

In this study, network pharmacology was combined to explore the potential mechanism of baicalin in alleviating neuronal ferroptosis after SAH by Western blot, qPCR, DHE probe, TMRE probe, and transmission electron microscopy in in vivo and in vitro SAH models.

The results of network pharmacology showed that baicalin mainly acted on the ferroptosis marker PTGS2, and the results of KEGG analysis suggested that the effect of baicalin in attenuating ferroptosis might be realized by activating the PI3K/AKT pathway. Baicalin partially restored the SAH-induced reduction of GPX4 expression and effectively suppressed the upregulation of NLRP3. These effects were abolished by the PI3K/AKT inhibitor LY294002. Baicalin was found to be effective in improving neurological function in mice in an in vivo SAH model.

This study demonstrated that baicalin attenuates neuronal ferroptosis after SAH by activating the PI3K/AKT pathway, which in turn upregulates GPX4 and suppresses NLRP3. These findings offer new insights into the pharmacological treatment of neuronal ferroptosis following SAH.

Baicalin can alleviate ferroptosis after SAH by activating the PI3K/AKT pathway.