The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms.

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms.
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DOI:
10.1155/2011/718302
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发表时间:
2011
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Shin HK
Shin HK
中科院分区:
其他
文献类型:
--
作者:
Kim JH;Park SH;Kim YW;Ha JM;Bae SS;Lee GS;Cho SI;Choi BT;Shin HK

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Dangkwisoo-San(DS)是一种草药提取物,在韩国传统医学中被广泛用于通过促进血液循环和缓解血瘀来治疗创伤性瘀斑和疼痛。然而,DS在脑血管疾病中的作用尚未进行实验研究。在小鼠局灶性脑缺血模型上研究了DS的保护作用。DS刺激人脑微血管内皮细胞(HBMEC)产生一氧化氮(NO)。DS(10-300 μg/mL)对小鼠主动脉有浓度依赖性舒张作用,一氧化氮合酶(NOS)抑制剂L-NAME可显著减弱DS的舒张作用,提示DS通过NO依赖性机制舒张血管。DS增加了静息脑血流量(CBF),尽管它引起轻度低血压。为探讨DS对C57/BL 6 J小鼠急性脑损伤的影响,采用大脑中动脉闭塞90 min,再灌注22.5 h的方法。动脉闭塞前3天给予DS与溶剂治疗相比,脑梗死面积显著减少53.7%。然而,DS并没有减少脑梗死的小鼠治疗相对特异性内皮NOS(eNOS)抑制剂,N5-(1-亚氨基乙基)-L-鸟氨酸,这表明DS的神经保护作用主要是内皮依赖性的。这与DS治疗小鼠脑中eNOS磷酸化增加有关。DS在eNOS依赖性血管舒张中急性改善CBF,并减少局灶性脑缺血的梗死面积。这些数据提供了因果关系的证据,DS是通过eNOS依赖性的NO的产生,改善血液循环,从而保护肾脏。
Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.
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