Protective effects of purified safflower extract on myocardial ischemia in vivo and in vitro
Protective effects of purified safflower extract on myocardial ischemia in vivo and in vitro
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DOI：
10.1016/j.phymed.2009.02.019
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发表时间：
2009-08-01
期刊：
影响因子：
7.9
通讯作者：
Tu, Peng-Fei
中科院分区：
文献类型：
--
作者：
Han, Shu-Yan;Li, Hai-Xia;Tu, Peng-Fei
Carthamus Tinctorius L.（红花）是临床上预防和治疗心脏病最常用的中草药之一。然而，这种保护作用的机制在很大程度上仍然未知。在这项研究中，我们研究了一种纯化的提取物C tinctorius（ECT）的抗心肌缺血作用在体内和体外。采用冠状动脉左前降支结扎法建立大鼠心肌缺血损伤模型。ECT预处理（100、200、400、600 mg/kg体重）可以通过限制梗死面积和改善心脏功能来保护心脏免受缺血损伤。在体外实验中，新生大鼠心室肌细胞孵育，以测试ECT对H2 O2暴露的直接细胞保护作用。在H2 O2暴露之前用100-400 μ g/ml ECT预处理显著增加细胞活力，如3（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑（MTT）测定所揭示。流式细胞仪Annexin V和PI双标记检测显示ECT也能明显抑制H2 O2诱导的心肌细胞凋亡。用2 '，7'-二氯荧光素二乙酸酯（DCFH-DA）检测细胞内活性氧（ROS）水平，ECT预处理可显著抑制H2 O2诱导的ROS升高。我们对ECT介导的抗凋亡作用中涉及的信号级联进行了初步研究。磷脂酰肌醇3激酶（PI 3 K）抑制剂（LY 294002）阻断ECT的细胞保护作用。综上所述，我们的研究结果提供了第一个证据表明，ECT在心肌缺血中的心脏保护作用部分是通过减少氧化应激诱导的损伤和细胞凋亡来实现的。这种保护作用是通过清除ROS和介导PI 3 K信号通路实现的。(C)2009年Elsevier GmbH。All rights reserved.
Carthamus tinctorius L. (safflower) is one of the most commonly used Chinese herbal medicines to prevent and treat cardiac disease in clinical practice. However, the mechanisms responsible for such protective effects remain largely unknown. In this study, we investigated the anti-myocardial ischemia effects of a purified extract of C tinctorius (ECT) both in vivo and in vitro. An animal model of myocardial ischemia injury was induced by left anterior descending coronary artery occlusion in adult rats. Pretreatment with ECT (100, 200, 400, 600 mg/kg body wt.) could protect the heart from ischemia injury by limiting infarct size and improving cardiac function. In the in vitro experiment, neonatal rat ventricular myocytes were incubated to test the direct cytoprotective effect of ECT against H2O2 exposure. Pretreatment with 100-400 mu g/ml ECT prior to H2O2 exposure significantly increased cell viability as revealed by 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. ECT also markedly attenuated H2O2-induced cardiomyocyte apoptosis, as detected by Annexin V and PI double labeling with flow cytometry. The intracellular level of reactive oxygen species (ROS) was shown by 2',7'-dichlorofluorescin diacetate (DCFH-DA), and ECT pretreatment significantly inhibited H2O2-induced ROS increase. We made a preliminary examination of the signaling cascade involved in ECT mediated anti-apoptotic effects. Phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) blocked the cytoprotective effect conferred by ECT. Taken together, our findings provide the first evidence that the cardioprotective effects of ECT in myocardial ischemia operate partially through reducing oxidative stress induced damage and apoptosis. The protection is achieved by scavenging of ROS and mediating the PI3K signaling pathway. (C) 2009 Elsevier GmbH. All rights reserved.