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

• Published in: Chemical biology & drug design Vol. 103; no. 2
• Main Authors: Dai, Weiwei, Yue, Chunjing, Zhang, Xiancai, Jia, Yalian, Han, Zongqi, Du, Jingxia, Song, Xiaohua
• Format: Journal Article
• Language: English
• Published: 01-02-2024
• Subjects: ACSL4; baicalin; ischemic stroke; miR‐556‐3p; OGD/R
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14455

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.
Baicalin alleviates OGD/R‐induced SK‐N‐SH cell apoptosis, inflammation, and ferroptosis in vitro, and brain injury in MCAO mice in vivo, via the regulation of miR‐556‐3p/ACSL4 pathway.