Wang Chaoyun, Zhang Dalei, Ma Hongmei, Liu Juntian
Xi'an Jiaotong University School of Medicine, Xi'an Shaanxi 710061, PR China.
Eur J Pharmacol. 2007 Dec 22;577(1-3):58-63. doi: 10.1016/j.ejphar.2007.08.033. Epub 2007 Sep 11.
Emodin-8-O-beta-D-glucoside extracted from the traditional Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc is widely used to treat acute hepatitis possibly by antioxidative mechanisms. The present study was designed to investigate whether emodin-8-O-beta-D-glucoside exerted neuroprotective effects on the focal cerebral injury induced by ischemia and reperfusion in vivo and on the neuronal damage induced by glutamate in vitro, and to study the possible mechanisms. Male Wistar rats were used to establish the model of ischemia and reperfusion. The behavioral test was performed and the cerebral infarction area was assessed in the brain slices stained with 2% 2,3,5-triphenyl tetrazolium chloride to evaluate the neuroprotective effects of emodin-8-O-beta-D-glucoside. Superoxide dismutase (SOD) activity, total antioxidative capability and malondialdehyde (MDA) level in the brain tissue were determined with spectrophotometrical methods to probe the primary mechanisms of emodin-8-O-beta-D-glucoside. In vitro, the neuroprotective effects of emodin-8-O-beta-D-glucoside were tested in the cultured cortical cells of fetal rats exposed to glutamate. Emodin-8-O-beta-D-glucoside concentration in plasma and brain tissue was also measured to examine distribution of emodin-8-O-beta-D-glucoside in the brain. The results showed that the treatment of rats with emodin-8-O-beta-D-glucoside reduced the neurological deficit score and the cerebral infarction area, increased SOD activity and total antioxidative capability, and decreased MDA level in the brain tissue in dose-dependent way. Emodin-8-O-beta-D-glucoside also inhibited the neuronal damage induced by glutamate. Besides, emodin-8-O-beta-D-glucoside was able to penetrate blood-brain barrier and distribute in the brain tissue. These findings demonstrate that emodin-8-O-beta-D-glucoside is able to provide neuroprotection against cerebral ischemia-reperfused injury and glutamate induced neuronal damage through exerting antioxidative effects and inhibiting glutamate neurotoxicity.
从传统中药虎杖中提取的大黄素-8-O-β-D-葡萄糖苷被广泛用于治疗急性肝炎，其作用机制可能与抗氧化有关。本研究旨在探讨大黄素-8-O-β-D-葡萄糖苷对体内缺血再灌注诱导的局灶性脑损伤以及体外谷氨酸诱导的神经元损伤是否具有神经保护作用，并研究其可能的机制。选用雄性Wistar大鼠建立缺血再灌注模型。进行行为学测试，并用2% 2,3,5-三苯基四氮唑氯化物染色的脑片评估脑梗死面积，以评价大黄素-8-O-β-D-葡萄糖苷的神经保护作用。采用分光光度法测定脑组织中超氧化物歧化酶（SOD）活性、总抗氧化能力和丙二醛（MDA）水平，以探究大黄素-8-O-β-D-葡萄糖苷的主要作用机制。在体外，检测大黄素-8-O-β-D-葡萄糖苷对暴露于谷氨酸的胎鼠皮质培养细胞的神经保护作用。同时测定血浆和脑组织中大黄素-8-O-β-D-葡萄糖苷的浓度，以检测其在脑中的分布情况。结果表明，用大黄素-8-O-β-D-葡萄糖苷治疗大鼠可降低神经功能缺损评分和脑梗死面积，增加SOD活性和总抗氧化能力，并以剂量依赖的方式降低脑组织中的MDA水平。大黄素-8-O-β-D-葡萄糖苷还可抑制谷氨酸诱导的神经元损伤。此外，大黄素-8-O-β-D-葡萄糖苷能够穿透血脑屏障并分布于脑组织中。这些研究结果表明，大黄素-8-O-β-D-葡萄糖苷能够通过发挥抗氧化作用和抑制谷氨酸神经毒性，对脑缺血再灌注损伤和谷氨酸诱导的神经元损伤提供神经保护。
