Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway.
Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway.
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DOI：
10.1016/j.lfs.2011.02.011
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发表时间：
2011-04
期刊：
影响因子：
6.1
通讯作者：
Y. Tsutsumi;R. Tsutsumi;K. Mawatari;Y. Nakaya;Michiko Kinoshita;Katsuya Tanaka;S. Oshita
中科院分区：
文献类型：
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作者：
Y. Tsutsumi;R. Tsutsumi;K. Mawatari;Y. Nakaya;Michiko Kinoshita;Katsuya Tanaka;S. Oshita
AIMS 化合物 K（C-K；20-O-d-吡喃葡萄糖基-20(S)-原人参二醇）是一种由肠道细菌形成的新型人参皂苷代谢物，天然存在于人参中。在本研究中，我们探讨了C-K给药是否对心肌缺血再灌注损伤具有保护作用及其潜在机制。主要方法我们使用体内缺血再灌注损伤小鼠模型，并在离体心脏中进行生化检测。关键发现与对照组相比，缺血再灌注后SC-K减少了梗死面积。免疫印迹分析表明，C-K 显着增强蛋白激酶 B (Akt) 和内皮一氧化氮合酶 (eNOS) 活性。 Wortmannin 是一种磷酸肌醇 3-激酶 (PI3K) 抑制剂，可阻断体内心脏保护作用并减弱 Akt 和 eNOS 的磷酸化。此外，C-K 预处理小鼠的心脏显示出对 Ca2+ 诱导的线粒体肿胀的抑制作用。 意义本研究表明，Compound K 预处理对心肌缺血再灌注损伤具有保护作用，部分是通过介导 PI3K 通路的激活以及 Akt 和 eNOS 的磷酸化来实现的。
AIMSCompound K (C-K; 20-O-d-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginsenoside metabolite formed by intestinal bacteria and does not occur naturally in ginseng. In this study, we investigated whether administration of C-K has protective effects on myocardial ischemia-reperfusion injury and its potential mechanisms.MAIN METHODSWe used in vivo mouse models of ischemia-reperfusion injury and performed biochemical assays in excised hearts.KEY FINDINGSC-K reduced infarct size compared with the control group after ischemia-reperfusion. Immunoblot analysis showed that C-K significantly enhanced protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) activity. Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked cardiac protection in vivo and attenuated phosphorylation of Akt and eNOS. Additionally, the hearts of C-K pretreated mice showed inhibition of mitochondrial swelling induced by Ca2+.SIGNIFICANCEThis study showed that Compound K pretreatment has protective effects on myocardial ischemia-reperfusion injury, partly by mediating the activation of PI3K pathway and phosphorylation of Akt and eNOS.