Senkyunolide A Attenuates OGD/R-Induced HT22 Cell Injury by Inhibiting Oxidative Stress and Apoptosis

Abstract This study aimed to investigate the protective effect and mechanism of Senkyunolide A (SenA) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in mouse hippocampal neuronal HT22 cells, providing experimental evidence for elucidating the application of SenA in the prevention and treatment of cerebral ischemia–reperfusion injury. An HT22 cell injury model was established using the OGD/R method and divided into the Control group, Model (OGD/R) group, Edaravone (EDA) group (OGD/R + EDA), and SenA group (OGD/R + SenA). Cell viability was detected by Cell counting kit-8 (CCK-8) assay; live and dead cells were observed by Calcein AM/PI cell viability assay kit (Calcein-AM/PI) double staining; intracellular reactive oxygen species (ROS) levels were measured using the H2DCFDA (DCFH-DA) fluorescent probe; levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined by biochemical kits; apoptosis rate was detected by flow cytometry; protein expression levels of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and Cysteine-dependent aspartate-specific protease-3 (Caspase-3) were measured by Western blot. Compared with the Control group, the OGD/R group showed significantly reduced cell viability (p < 0.001), increased proportions of dead cells, ROS and MDA levels, and apoptosis rate (p < 0.001), decreased SOD activity and GSH levels (p < 0.05; p < 0.001), significantly upregulated protein expression of Bax and Caspase-3 (p < 0.01; p < 0.001), and downregulated Bcl-2 expression (p < 0.001). Compared with the OGD/R group, both SenA and EDA significantly increased cell viability (p < 0.001), reduced the proportion of dead cells, ROS and MDA levels, and apoptosis rate (p < 0.001), upregulated SOD activity and GSH levels (p < 0.01; p < 0.001), downregulated protein expression of Bax and Caspase-3 (p < 0.01; p < 0.001), and upregulated Bcl-2 expression (p < 0.001). SenA can alleviate OGD/R-induced neuronal injury by mitigating oxidative stress and inhibiting cell apoptosis. This study provides modern experimental evidence for the traditional theory of Chuanxiong in “promoting blood circulation, removing blood stasis, and unblocking brain collaterals,” and offers new insights for the prevention and treatment of ischemia–reperfusion brain injury with traditional Chinese medicine.