Abstract
BACKGROUND: Inflammation is involved in cerebral ischemia/reperfusion (I/R)-induced neurological damage. Saikosaponin A (SSa), extracted from Radix bupleuri, has been reported to exert anti-inflammatory effects. This article aimed to investigate whether SSa could ameliorate neuroinflammation mediated by ischemic stroke and the underlying mechanism. METHODS: Rat middle cerebral artery occlusion (MCAO) model was employed in this study, and the cognitive and motor functions were detected by behavioral tests. Inflammatory cytokines in the serum were detected by ELISA kits. The expression levels of Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and high-mobility group box 1 (HMGB1) in the brain tissues were assayed with Western blot. RESULTS: Our results showed that SSa pretreatment could significantly reduce brain damage, improve neurological function recovery, and decrease the water content of brain tissues when compared with the model group. SSa pretreatment significantly reduced the serum HMGB1 level and downregulated the contents of inflammatory cytokines including tumor necrosis factor-α, interleukin-1 beta, and interleukin-6. Furthermore, SSa pretreatment could attenuate the decreased TLR4 and nucleus NF-κB in the brain of MCAO rats. The protein level of HMGB1 in the nucleus was significantly upregulated in the SSa pretreatment group. CONCLUSION: Our results suggested that the pretreatment with SSa provided significant protection against cerebral I/R injury in rats via its anti-inflammation property by inhibiting the nucleus HMGB1 release.