Neuroprotective Effect of Sanguisorbae Radix against Oxidative Stress-Induced Brain Damage: in Vitro and in Vivo
Neuroprotective Effect of Sanguisorbae Radix against Oxidative Stress-Induced Brain Damage: in Vitro and in Vivo
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DOI：
10.1248/bpb.31.2028
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发表时间：
2008-11-01
影响因子：
2
通讯作者：
Seong, Yeon Hee
中科院分区：
文献类型：
--
作者：
Nguyen, Thi Thuy Ha;Cho, Soon Ock;Seong, Yeon Hee
地榆 (SR) 是地榆（蔷薇科）的根，在韩国传统上因其抗炎、抗感染和镇痛活性而被使用。先前的研究表明，SR 可防止 A beta (25-35) 在培养的大鼠皮质神经元中诱导的神经细胞损伤。本研究旨在进一步研究 SR 对大鼠皮质神经元原代培养物中氧化应激诱导的毒性以及大鼠缺血诱导的脑损伤的神经保护作用。 SR在1050μg/ml的浓度范围内，抑制H2O2（100μM）诱导的神经元死亡，这种死亡被N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801（5μM）和L型Ca2+通道阻滞剂维拉帕米（20μM）显着抑制。 SR (10-50 μg/ml)、MK-801 (5 μM) 和维拉帕米 (20 μM) 预处理可抑制 H2O2 诱导的细胞内 Ca2+ 浓度 ([Ca2+](i)) 升高（通过荧光染料 Fluo-4 AM 测量）。 SR (10-50 μg/ml) 抑制 H2O2 诱导的谷氨酸释放到培养基中（通过 HPLC 测量），并抑制活性氧 (ROS) 的产生（通过 2',7'-二氯二氢荧光素二乙酸酯 (H(2)DCFDA) 测量）。在体内，SR 可预防由 2 小时大脑中动脉闭塞 (MCAO) 和 24 小时再灌注引起的脑缺血损伤。接受SR（10、30mg/kg，口服）的大鼠的缺血性梗塞和水肿显着减少，神经功能也相应改善。从 SR 中分离出的儿茶素可抑制培养物中 H2O2 诱导的神经元死亡。综上所述，这些结果表明SR通过干扰[Ca2+](i)的增加、抑制谷氨酸的释放和ROS的产生来抑制H2O2诱导的神经元死亡，并且SR对局灶性脑缺血损伤的神经保护作用是由于其抗氧化作用。因此，SR 可能对中风等神经退行性疾病具有治疗作用。
Sanguisorbae radix (SR), the root of Sanguisorba officinalis L. (Rosaceae), has been traditionally used for its anti-inflammatory, anti-infectious and analgesic activities in Korea. Previous work has shown that SR prevents neuronal cell damage induced by A beta (25-35) in cultured rat cortical neurons. The present study was carried out to further investigate the neuroprotective effect of SR on oxidative stress-induced toxicity in primary culture of rat cortical neurons, and on ischemia-induced brain damage in rats. SR, over a concentration range of 1050 mu g/ml, inhibited H2O2 (100 mu M)-induced neuronal death, which was significantly inhibited by MK-801 (5 mu M) an N-methyl-D-aspartate (NMDA) receptor antagonist, and verapamil (20 mu M), an L-type Ca2+ channel blocker. Pretreatment of SR (10-50 mu g/ml), MK-801 (5 mu M), and verapamil (20 mu M) inhibited H2O2-induced elevation of intracellular Ca2+ concentration ([Ca2+](i)) measured by a fluorescent dye, Fluo-4 AM. SR (10-50 mu g/ml) inhibited H2O2-induced glutamate release into medium measured by HPLC, and generation of reactive oxygen species (ROS) measured by 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA). In vivo, SR prevented cerebral ischemic injury induced by 2-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct and edema were significantly reduced in rats that received SR (10, 30 mg/kg, orally), with a corresponding improvement in neurological function. Catechin isolated from SR inhibited H2O2-induced neuronal death in cultures. Taken together, these results suggest that SR inhibits H2O2-induced neuronal death by interfering with the increase of [Ca2+](i), and inhibiting glutamate release and generation of ROS, and that the neuroprotective effect of SR against focal cerebral ischemic injury is due to its anti-oxidative effects. Thus SR might have therapeutic roles in neurodegenerative diseases such as stroke.