Salvianolic acid A prevented neuroinflammation and apoptosis caused by acute ischemic stroke through inhibiting the HMGB1/NF-κB signaling pathway

Neuroinflammation plays a role in the overall pathophysiological process of stroke. Developing preventive stroke drugs that target neuroinflammation may be a promising strategy. The aim of our study was to investigate the effect of salvianolic acid A (SAA) administered preventively on the regulation of neuroinflammation and apoptosis and to evaluate its underlying mechanisms during stroke. An autologous thrombus stroke model was established in SD rats using electrocoagulation, and an oxygen-glucose deprivation (OGD) injury model was created in human brain microvascular endothelial cells (HBMECs). SAA (10 mg/kg) was administered orally twice a day for 5 days prior to the operation. The supernatant of lipopolysaccharide (LPS) -treated BV2 cells was used as conditioned medium (CM). HBMECs were co-cultured with CM for 6 h. Our results showed that pretreatment with SAA alleviated cerebral infarction, decreased the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), inhibited the polarization of M1 microglia, promoted the polarization of M2 microglia, inhibited apoptosis, and balanced the expression of Bax and Bcl-2 proteins both in vivo and in vitro. Furthermore, we found that SAA inhibited the activation of the HMGB1/NF-κB signaling pathway. In conclusion, our results indicate that SAA prevents neuroinflammation and apoptosis caused by acute ischemic stroke through the inhibition of the HMGB1/NF-κB signaling pathway. Pretreatment with SAA is a potential strategy for the prevention of ischemic stroke.