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在绿茶主要儿茶素表没食子儿茶素没食子酸酯的体外心电图和心脏离子通道效应。

In vitro electrocardiographic and cardiac ion channel effects of (-)-epigallocatechin-3-gallate, the main catechin of green tea.

机构信息

Disposition, Safety, and Animal Research, Sanofi-Aventis US Inc., Bridgewater, New Jersey 08807, USA.

出版信息

J Pharmacol Exp Ther. 2010 Aug;334(2):619-26. doi: 10.1124/jpet.110.169391. Epub 2010 May 18.

Abstract

Epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea. EGCG is also available for consumption in the form of concentrated over-the-counter nutritional supplements. This compound is currently undergoing clinical trials for the treatment of a number of diseases including multiple sclerosis, and a variety of cancers. To date, few data exist regarding the effects of EGCG on the electrophysiology of the heart. Therefore, we examined the effects of EGCG on the electrocardiogram recorded from Langendorff-perfused guinea pig hearts and on cardiac ion channels using patch-clamp electrophysiology. EGCG had no significant effects on the electrocardiogram at concentrations of 3 and 10 microM. At 30 microM, EGCG prolonged PR and QRS intervals, slightly shortened the QT interval, and altered the shape of the ST-T-wave segment. The ST segment merged with the upstroke of the T wave, and we noted a prolongation in the time from the peak of the T wave until the end. Patch-clamp studies identified the KvLQT1/minK K(+) channel as a target for EGCG (IC(50) = 30.1 microM). In addition, EGCG inhibited the cloned human cardiac Na(+) channel Na(v)1.5 in a voltage-dependent fashion. The L-type Ca(2+) channel was inhibited by 20.8% at 30 microM, whereas the human ether-a-go-go-related gene and Kv4.3 cardiac K(+) channels were less sensitive to inhibition by EGCG. ECGC has a number of electrophysiological effects in the heart, and these effects may have clinical significance when multigram doses of this compound are used in human clinical trials or through self-ingestion of large amounts of over-the-counter products enriched in EGCG.

摘要

表没食子儿茶素没食子酸酯(EGCG)是绿茶中主要的儿茶素。EGCG 也以浓缩的非处方营养补充剂形式供消费。这种化合物目前正在进行临床试验,用于治疗多种疾病,包括多发性硬化症和多种癌症。迄今为止,关于 EGCG 对心脏电生理学的影响的数据很少。因此,我们使用膜片钳电生理学研究了 EGCG 对 Langendorff 灌注豚鼠心脏记录的心电图和心脏离子通道的影响。在 3 和 10 μM 的浓度下,EGCG 对心电图没有显著影响。在 30 μM 时,EGCG 延长 PR 和 QRS 间隔,略微缩短 QT 间隔,并改变 ST-T 波段的形状。ST 段与 T 波的上升融合,我们注意到 T 波峰值到终点的时间延长。膜片钳研究确定 KvLQT1/minK K(+)通道是 EGCG 的靶点(IC(50) = 30.1 μM)。此外,EGCG 以电压依赖性方式抑制克隆的人心脏 Na(+)通道 Na(v)1.5。在 30 μM 时,L 型钙(Ca(2+))通道被抑制了 20.8%,而人醚-a-鹅-鹅相关基因和 Kv4.3 心脏 K(+)通道对 EGCG 的抑制作用不太敏感。EGCG 在心脏中具有多种电生理作用,当这种化合物在人体临床试验中使用或通过自我摄入富含 EGCG 的大量非处方产品时,这些作用可能具有临床意义。

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