Zhuang Hean, Kim Yun-Sook, Koehler Raymond C, Doré Sylvain
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Ann N Y Acad Sci. 2003 May;993:276-86; discussion 287-8. doi: 10.1111/j.1749-6632.2003.tb07534.x.
Polyphenolic compounds, such as resveratrol, are naturally present at high concentration in grape skin, seeds, and red wine. Resveratrol is present in cis and trans isoforms and the major trans isomer is the biologically active one. Epidemiologic studies have revealed a reduced incidence of cardiovascular risk associated with consumers of red wine; this has been popularized as the French paradox. Resveratrol has been shown to have significant antioxidant properties in a variety of in vitro and in vivo models. It can reduce ischemic damage in heart ischemia reperfusion injury and also in brain ischemia/reperfusion in rodent models. Due to the high rate of oxygen consumption in the brain, and especially low levels of antioxidant defense enzymes, this organ is particularly susceptible of free radical damage. Most of the protective biological actions associated with resveratrol have been associated with its intrinsic radical scavenger properties. We have investigated the possibility of other indirect pathways by which resveratrol can exert its neuroprotective abilities. We have specifically tested whether heme oxygenase neuroprotective enzyme could be stimulated after resveratrol treatment. Using primary neuronal cultures, resveratrol was able to significantly induce heme oxygenase 1, whereas vehicle control showed no effect. No detectable toxicity was quantified. It is well established that after stroke significant levels of intracellular heme levels increase. The source of free heme comes mainly from several heme-containing enzymes. Heme (iron-protoporphyrin IX) is a pro-oxidant and its rapid degradation by heme oxygenase is believed to be protective. Moreover, the generation of heme metabolites can also have their own intrinsic cellular properties. All together, increased heme oxygenase activity by resveratrol is a unique pathway by which this compound can exert its neuroprotective actions.
多酚类化合物，如白藜芦醇，在葡萄皮、葡萄籽和红酒中天然存在且浓度很高。白藜芦醇有顺式和反式异构体，主要的反式异构体具有生物活性。流行病学研究表明，饮用红酒的人群心血管疾病风险发生率降低；这一现象被称为“法国悖论”。在多种体外和体内模型中，白藜芦醇已被证明具有显著的抗氧化特性。在啮齿动物模型中，它可以减轻心脏缺血再灌注损伤以及脑缺血/再灌注损伤中的缺血性损伤。由于大脑的耗氧率很高，尤其是抗氧化防御酶水平较低，这个器官特别容易受到自由基损伤。与白藜芦醇相关的大多数保护生物学作用都与其内在的自由基清除特性有关。我们研究了白藜芦醇发挥神经保护作用的其他间接途径的可能性。我们特别测试了白藜芦醇处理后是否能刺激血红素加氧酶这种神经保护酶。使用原代神经元培养物，白藜芦醇能够显著诱导血红素加氧酶1，而溶剂对照组则无此作用。未检测到可量化的毒性。众所周知，中风后细胞内血红素水平会显著升高。游离血红素的来源主要是几种含血红素的酶。血红素（铁原卟啉IX）是一种促氧化剂，其被血红素加氧酶快速降解被认为具有保护作用。此外，血红素代谢产物的生成也可能具有其自身固有的细胞特性。总之，白藜芦醇提高血红素加氧酶活性是该化合物发挥神经保护作用的一条独特途径。
