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红景天苷及其类似物酪醇半乳糖苷对体内局灶性脑缺血和 H2O2 诱导的体外神经毒性的神经保护作用。

Neuroprotective effects of Salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and H2O2-induced neurotoxicity in vitro.

机构信息

Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Neurotox Res. 2012 May;21(4):358-67. doi: 10.1007/s12640-011-9290-7. Epub 2011 Nov 18.

Abstract

Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L. that elicits neuroprotective effects in vivo and in vitro. Tyrosol galactoside (Tyr), an analog of Sal, was recently synthesized in our laboratory. The purpose of the current study was to investigate and compare the neuroprotective effects of Sal and Tyr against focal cerebral ischemia in vivo and H(2)O(2)-induced neurotoxicity in vitro. Sal and Tyr significantly prevented a cerebral ischemic injury induced by a 2 h middle cerebral artery occlusion and a 24 h reperfusion in rats in vivo. Furthermore, the oxidative insult was markedly attenuated by treatments of Sal and Tyr in the cultured rat cortical neurons after a 30 min exposure to 50 μM of H(2)O(2). Western blot analysis revealed that Sal and Tyr decreased the expression of Bax and restored the balance of pro- and anti-apoptotic proteins. The neuroprotective effects of these two analogues show that Tyr has a better antioxidative action compared with Sal both in vivo and in vitro, and suggest that the antioxidant activity of Sal and Tyr may be partly due to their different substituents in their glycosyl groups. This gives a new insight into the development of therapeutic natural antioxidants against oxidative stress.

摘要

红景天苷(Sal)是从红景天的根中提取的天然抗氧化剂,具有体内和体外的神经保护作用。我们实验室最近合成了红景天苷的类似物——酪醇半乳糖苷(Tyr)。本研究旨在探讨和比较 Sal 和 Tyr 对体内局灶性脑缺血和体外 H2O2 诱导的神经毒性的神经保护作用。Sal 和 Tyr 可显著预防大鼠体内 2 小时大脑中动脉闭塞和 24 小时再灌注引起的脑缺血损伤。此外,在培养的大鼠皮质神经元中,用 50 μM H2O2 处理 30 分钟后,Sal 和 Tyr 明显减轻了氧化损伤。Western blot 分析表明,Sal 和 Tyr 降低了 Bax 的表达并恢复了促凋亡和抗凋亡蛋白的平衡。这两种类似物的神经保护作用表明,Tyr 在体内和体外均具有比 Sal 更好的抗氧化作用,这提示 Sal 和 Tyr 的抗氧化活性可能部分归因于它们糖基取代基的不同。这为开发治疗氧化应激的天然抗氧化剂提供了新的思路。

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