School of Pharmacy, Yantai University, Yantai 264003, PR China.
Neuroscience. 2011 Sep 29;192:572-9. doi: 10.1016/j.neuroscience.2011.06.079. Epub 2011 Jul 1.
Recent studies have demonstrated nuclear factor-κB (NF-κB) and high-mobility group box1 (HMGB1) associated with the pathophysiology of cerebral ischemia. We isolated Curculigoside A, the major bioactive compound present in Curculigo orchioides. The objectives of this study were to determine the effects of Curculigoside A on cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic stroke in vivo. For oxygen-glucose deprivation and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were pre-incubated with Curculigoside A. For in vivo experiment, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, then followed by reperfusion for 23 h. Treatment of SH-SY5Y cells with Curculigoside A reduced the oxygen-glucose deprivation-induced cytotoxicity and apoptosis, blocked TNF-α-induced NF-κB and IκB-α phosphorylation, and decreased HMGB1 expression. At doses higher than 10 mg/kg, Curculigoside A produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). Curculigoside A (20 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h, and 5 h after I/R. Curculigoside A 20 mg/kg attenuated histopathological damage, decreased cerebral Evans Blue extravasation, inhibited NF-κB activation and reduced HMGB1 expression. These data show that Curculigoside A protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and NF-κB signaling pathway.
最近的研究表明，核因子-κB（NF-κB）和高迁移率族蛋白 1（HMGB1）与脑缺血的病理生理学有关。我们分离出了主要生物活性化合物毛蕊花糖苷 A，该化合物存在于毛蕊花属植物中。本研究的目的是确定毛蕊花糖苷 A 对体外培养的神经元细胞系 SH-SY5Y 以及体内实验性缺血性中风的影响。对于体外氧葡萄糖剥夺和肿瘤坏死因子-α（TNF-α）刺激的 SH-SY5Y 细胞系，SH-SY5Y 细胞先用毛蕊花糖苷 A 孵育。在体内实验中，大鼠大脑中动脉闭塞（MCAO） 1 小时，然后再灌注 23 小时。用毛蕊花糖苷 A 处理 SH-SY5Y 细胞可减少氧葡萄糖剥夺诱导的细胞毒性和凋亡，阻断 TNF-α诱导的 NF-κB 和 IκB-α磷酸化，并降低 HMGB1 表达。在高于 10 mg/kg 的剂量下，毛蕊花糖苷 A 在缺血再灌注（I/R）的大鼠中产生了显著的神经保护作用。毛蕊花糖苷 A（20 mg/kg）在 I/R 后 1 小时、3 小时和 5 小时延迟给药时表现出显著的神经保护活性。毛蕊花糖苷 A 20 mg/kg 减轻了组织病理学损伤，减少了脑伊文思蓝外渗，抑制了 NF-κB 激活，降低了 HMGB1 表达。这些数据表明，毛蕊花糖苷 A 通过减轻脑 I/R 损伤和减弱血脑屏障（BBB）破坏来保护大脑免受 I/R 损伤，具有有利的治疗时间窗，其保护作用可能涉及 HMGB1 和 NF-κB 信号通路。
