Baicalin alleviates oxygen-glucose deprivation/reoxygenation-induced SK-N-SH cell injury via the regulation of miR-556-3p/ACSL4 pathway

Baicalin (BCL) has been found to have neuroprotective effects in ischemic stroke (IS), but its underlying molecular mechanisms are unknown. SK-N-SH cells were treated with BCL and then induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Cell proliferation, apoptosis, inflammation, and ferroptosis were detected. Protein levels were examined by western blot. The expression levels of microRNA (miR)-556-3p and ACSL4 were tested via quantitative real-time PCR. MiR-556-3p and Acyl-CoA synthetase long-chain family member 4 (ACSL4) interaction was confirmed via dual-luciferase reporter assay and RNA pull-down assay. Middle cerebral artery occlusion (MCAO) mice model was constructed to assess the role of BCL on brain injury in vivo. Our study showed that BCL treatment alleviated OGD/R-induced SK-N-SH cell apoptosis, inflammation and ferroptosis. MiR-556-3p was decreased in OGD/R-induced SK-N-SH cells, and BCL treatment enhanced its expression. MiR-556-3p could target ACSL4, and its overexpression relieved OGD/R-induced SK-N-SH cell injury by targeting ACSL4. Besides, miR-556-3p inhibitor or ACSL4 overexpression reversed the inhibitory effect of BCL on OGD/R-induced SK-N-SH cell injury. In vivo, BCL alleviated brain injury in MCAO mice through miR-556-3p/ACSL4 axis. In conclusion, BCL alleviated OGD/R-induced SK-N-SH cell injury and relieved brain injury in MCAO mice by regulating miR-556-3p/ACSL4 axis.