State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
Eur J Pharmacol. 2013 Aug 15;714(1-3):303-11. doi: 10.1016/j.ejphar.2013.07.036. Epub 2013 Jul 30.
Transient cerebral ischemia initiates a complex series of inflammatory events, which has been associated with an increase in behavioral deficits and secondary brain damage. Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that Ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) activation in anti-inflammatory pathways. We hypothesized that Ruscogenin protects against brain ischemia by inhibiting NF-κB-mediated inflammatory pathway. To test this hypothesis, adult male mice (C57BL/6 strain) were pretreated with Ruscogenin and then subjected to transient middle cerebral artery occlusion (MCAO)/reperfusion. After 1 h MCAO and 24 h reperfusion, neurological deficit, infarct sizes, and brain water content were measured. Ruscogenin markedly decreased the infarct size, improved neurological deficits and reduced brain water content after MCAO. The activation of NF-κB Signaling pathway was observed after 1h of ischemia and 1h of reperfusion, and Ruscogenin significantly inhibited NF-κB p65 expression, phosphorylation and translocation from cytosol to nucleus at this time point in a dose-dependent manner. NF-κB DNA binding activity, and the expression of NF-κB target genes, including ICAM-1, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were also suppressed by Ruscogenin pretreatment after 1 h MCAO and 24 h reperfusion. The results indicated that Ruscogenin protected the brain against ischemic damage caused by MCAO, and this effect may be through downregulation of NF-κB-mediated inflammatory responses.
短暂性脑缺血引发了一系列复杂的炎症事件，这些炎症事件与行为缺陷的增加和继发性脑损伤有关。鲁斯可苷元是一种主要的甾体皂素，存在于传统中药麦冬中，具有多种生物活性。最近的研究表明，鲁斯可苷元参与下调细胞间黏附分子-1（ICAM-1）和核因子-κB（NF-κB）在抗炎途径中的激活。我们假设鲁斯可苷元通过抑制 NF-κB 介导的炎症途径来保护大脑免受缺血的影响。为了验证这一假设，我们用鲁斯可苷元预处理成年雄性小鼠（C57BL/6 品系），然后进行短暂性大脑中动脉闭塞（MCAO）/再灌注。MCAO 1 小时和再灌注 24 小时后，测量神经功能缺损、梗死面积和脑含水量。鲁斯可苷元明显减少了 MCAO 后的梗死面积，改善了神经功能缺损，降低了脑含水量。在缺血 1 小时和再灌注 1 小时后观察到 NF-κB 信号通路的激活，鲁斯可苷元以剂量依赖的方式显著抑制 NF-κB p65 的表达、磷酸化和从细胞质向核内的易位。NF-κB DNA 结合活性以及 NF-κB 靶基因的表达，包括 ICAM-1、诱导型一氧化氮合酶（iNOS）、环氧化酶（COX-2）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β），在 MCAO 后 1 小时和再灌注 24 小时后也被鲁斯可苷元预处理所抑制。这些结果表明，鲁斯可苷元可以保护大脑免受 MCAO 引起的缺血性损伤，这种作用可能是通过下调 NF-κB 介导的炎症反应。
