Shen Jia, Zhang Hongyin, Lin Han, Su Hui, Xing Dongming, Du Lijun
Laboratory of Pharmaceutical Sciences, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
Eur J Pharmacol. 2007 Mar 8;558(1-3):88-95. doi: 10.1016/j.ejphar.2006.11.059. Epub 2006 Dec 6.
Brazilein isolated from Caesalpinia sappan was evaluated for neuroprotection against transient focal cerebral ischemia/reperfusion in rats. The results showed that administration of brazilein after the onset of cerebral ischemia reperfusion can reduce the brain infarction area and improve the neurological score. The mechanisms underlying the action were investigated and attributed to the anti-inflammatory effect of brazilein, because a decrease of the mRNA level of pro-inflammatory cytokines (tumor necrosis factor-alpha(TNF-alpha) and interleukin-6 (IL-6)) was found in the ischemic animals with brazilein treatment. To further substantiate the anti-inflammatory effect of brazilein, we examined the mRNA expression of the cytokines in the lipopolysaccharide (LPS) induced microglial cell line BV2 cells; TNF-alpha and IL-6 mRNA expressions were significantly suppressed by brazilein treatment but the decrease of interleukin-1beta (IL-1beta) expression was not detected. Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS), another indicator of the inflammatory response of the immune cells was measured in RAW 264.7 macrophages and BV2 cells; brazilein inhibited its production induced by LPS in both types of cells in a dose-dependent manner. Consistently, the mRNA level of iNOS was also decreased by brazilein. Together, these results illustrate that brazilein can protect the brain against ischemia/reperfusion injury and the anti-inflammatory effect was believed to be one of the contributive mechanisms.
对从苏木中分离出的巴西苏木素进行了评估,以确定其对大鼠短暂性局灶性脑缺血/再灌注的神经保护作用。结果表明,在脑缺血再灌注发作后给予巴西苏木素可减少脑梗死面积并改善神经学评分。对该作用的潜在机制进行了研究,并归因于巴西苏木素的抗炎作用,因为在接受巴西苏木素治疗的缺血动物中发现促炎细胞因子(肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6))的mRNA水平降低。为了进一步证实巴西苏木素的抗炎作用,我们检测了脂多糖(LPS)诱导的小胶质细胞系BV2细胞中细胞因子的mRNA表达;巴西苏木素处理可显著抑制TNF-α和IL-6的mRNA表达,但未检测到白细胞介素-1β(IL-1β)表达的降低。在RAW 264.7巨噬细胞和BV2细胞中测量了诱导型一氧化氮合酶(iNOS)产生的一氧化氮(NO),这是免疫细胞炎症反应的另一个指标;巴西苏木素在两种细胞类型中均以剂量依赖性方式抑制LPS诱导的NO产生。一致地,巴西苏木素也降低了iNOS的mRNA水平。总之,这些结果表明巴西苏木素可以保护大脑免受缺血/再灌注损伤,并且抗炎作用被认为是其作用机制之一。