School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
Eur J Pharm Sci. 2012 Jan 23;45(1-2):50-7. doi: 10.1016/j.ejps.2011.10.019. Epub 2011 Nov 7.
There have been several studies of nuclear factor-κB (NF-κB) and high-mobility group box1 (HMGB1) associated with the pathophysiology of cerebral ischemia. Tricin 7-glucoside, a major bioactive compound extracted from Sedum sarmentosum Bunge. The objectives of this study were to determine the effects of Tricin 7-glucoside on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were incubated with Tricin 7-glucoside. For in vivo experiment, rats were subjected to middle cerebral artery occlusion (MACO) for 1h, then followed by reperfusion for 23 h. Treatment of SH-SY5Y cells with Tricin 7-glucoside reduced the OGD-induced apoptosis and cytotoxicity, blocked TNF-α-induced NF-κB and IκB-α phosphorylation, and decreased HMGB1 expression. At doses higher than 50mg/kg, Tricin 7-glucoside produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). Tricin 7-glucoside (100mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 2h and 4h after I/R. Tricin 7-glucoside 100mg/kg attenuated histopathological damage, decreased brain edema, inhibited NF-κB activation and reduced HMGB1 expression. These data show that Tricin 7-glucoside 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.
已有多项研究探讨了核因子-κB（NF-κB）和高迁移率族蛋白 B1（HMGB1）与脑缺血病理生理学的关系。山柰素 7-葡萄糖苷是从景天三七中提取的主要生物活性化合物。本研究旨在探讨山柰素 7-葡萄糖苷对体外培养神经元 SH-SY5Y 细胞系和体内实验性缺血性脑卒中的影响。对于体外氧葡萄糖剥夺（OGD）和肿瘤坏死因子-α（TNF-α）刺激的 SH-SY5Y 细胞系，用山柰素 7-葡萄糖苷孵育 SH-SY5Y 细胞。在体内实验中，大鼠大脑中动脉闭塞（MACO） 1h 后，再灌注 23h。山柰素 7-葡萄糖苷处理 SH-SY5Y 细胞可减少 OGD 诱导的细胞凋亡和细胞毒性，阻断 TNF-α诱导的 NF-κB 和 IκB-α磷酸化，并降低 HMGB1 表达。在 50mg/kg 以上剂量下，山柰素 7-葡萄糖苷对缺血再灌注（I/R）大鼠具有显著的神经保护作用。山柰素 7-葡萄糖苷（100mg/kg）在 I/R 后 2h 和 4h 延迟给药时，表现出显著的神经保护活性。山柰素 7-葡萄糖苷 100mg/kg 可减轻组织病理学损伤，降低脑水肿，抑制 NF-κB 激活，减少 HMGB1 表达。这些数据表明，山柰素 7-葡萄糖苷通过减轻脑缺血再灌注损伤和血脑屏障（BBB）破坏，对脑缺血再灌注损伤具有保护作用，其保护作用可能与 HMGB1 和 NF-κB 信号通路有关。
