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杜仲皮对过氧化氢诱导的 SH-SY5Y 神经元细胞死亡的保护作用。

Eucommia ulmoides Oliv. Bark. protects against hydrogen peroxide-induced neuronal cell death in SH-SY5Y cells.

机构信息

Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

出版信息

J Ethnopharmacol. 2012 Jul 13;142(2):337-45. doi: 10.1016/j.jep.2012.04.010. Epub 2012 May 14.

DOI:10.1016/j.jep.2012.04.010
PMID:22735663
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Eucommia ulmoides Oliv. Bark. (EUE), has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve the tone of liver and kidneys, and promote longevity the traditional tonic medicines of Korea, China, and Japan.

AIM OF THE STUDY

In this study, we investigated that the neuroprotective activities and possible mechanisms of EUE aqueous extract in hydrogen peroxide (H(2)O(2))-induced neuronal cell death in human SH-SY5Y neuroblastoma cells.

MATERIAL AND METHOD

We examined the effects of EUE against H(2)O(2)-induced cytotoxicity, DNA condensation, the production of reactive oxygen species (ROS), loss of mitochondria membrane potential (MMP), the proteolysis of cleaved poly-ADP-ribose polymerase (PARP), and the expression of Bcl-2, Bcl-xL, cleaved caspase-3, and release of cytochrome c. Moreover, we attempted to determine whether EUE suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), and phosphoinositide 3-kinase (PI3K)/Akt.

RESULTS

Pretreatment with EUE increased cell viability and inhibited cytotoxicity and DNA condensation. EUE also attenuated the increase in ROS production and MMP reduction. Western blot data revealed that EUE inhibited H(2)O(2)-induced up- or down-regulation of cleaved PARP, cleaved caspase-3, Bcl-2, and Bcl-xL. The EUE inhibited release of cytochrome c from mitochondria to the cytosol, and significantly attenuated H(2)O(2)-induced phosphorylation of JNK, p38 MAPK, ERK 1/2, and PI3K/Akt.

CONCLUSION

The potent neuroprotective capacity of EUE, shown in these experiments, may potentially be applied in the prevention or treatment of neurodegenerative diseases such as Alzheimer's disease (AD).

摘要

植物药用途

杜仲(Eucommia ulmoides Oliv. Bark.,EUE)在韩国、中国和日本传统的滋补药中,通常被用于增强肌肉和肺部功能、降低血压、防止流产、改善肝肾功能和延长寿命。

目的

本研究旨在探讨杜仲水提物对过氧化氢(H2O2)诱导的人 SH-SY5Y 神经母细胞瘤细胞死亡的神经保护作用及其可能机制。

材料和方法

我们检测了杜仲对 H2O2 诱导的细胞毒性、DNA 凝聚、活性氧(ROS)生成、线粒体膜电位(MMP)丧失、多聚(ADP-核糖)聚合酶(PARP)的切割、Bcl-2、Bcl-xL、切割的胱天蛋白酶-3(cleaved caspase-3)和细胞色素 c 释放的影响。此外,我们试图确定杜仲是否抑制 c-Jun N-末端激酶(JNK)、p38 丝裂原活化蛋白激酶(p38 MAPK)、细胞外信号调节激酶 1/2(ERK 1/2)和磷酸肌醇 3-激酶(PI3K)/Akt 的磷酸化。

结果

EUE 预处理可增加细胞活力并抑制细胞毒性和 DNA 凝聚。EUE 还可减轻 ROS 生成和 MMP 减少的增加。Western blot 数据显示,EUE 抑制 H2O2 诱导的切割型 PARP、切割型胱天蛋白酶-3、Bcl-2 和 Bcl-xL 的上调或下调。EUE 抑制细胞色素 c 从线粒体向细胞质的释放,并显著减弱 H2O2 诱导的 JNK、p38 MAPK、ERK 1/2 和 PI3K/Akt 的磷酸化。

结论

本实验表明,杜仲具有较强的神经保护能力,可能应用于阿尔茨海默病(AD)等神经退行性疾病的预防或治疗。

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