Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase
Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase
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DOI：
10.1016/j.vph.2012.06.002
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发表时间：
2012-09-01
影响因子：
4
通讯作者：
Kim, Chi Dae
中科院分区：
文献类型：
--
作者：
Park, Ji Young;Choi, Young Whan;Kim, Chi Dae
五味子素J （Gomisin J， GJ）是一种从五味子（Schisandra chinensis， SC）中提取的木脂素。五味子是韩国人熟知的改善心血管症状的药材。因此，本研究考察了GJ对血管的影响，并确定了其中的机制。大鼠胸主动脉暴露于GJ （1 ~ 30 μ g/ml）后，血管出现浓度依赖性松弛，且在内皮（ED）完好的主动脉中更为明显。一氧化氮合酶（NOS）抑制剂L-NAME预处理后，GJ诱导的ed依赖性松弛明显减弱。在完整的大鼠胸主动脉内皮细胞。GJ还能促进一氧化氮（NO）的产生。在使用人冠状动脉内皮细胞的研究中，GJ增强了内皮NOS (eNOS) Ser（1177）位点的磷酸化，增加了eNOS的细胞质易位，随后增加了NO的产生。GJ的这些作用不仅可以被EGTA和BAPTA-AM等钙螯合剂减弱，还可以被LY294002 （PI3K/Akt抑制剂）减弱，这表明GJ对eNOS的激活依赖于钙和PI3K/Akt。此外，GJ给药后细胞内钙水平立即升高，但Akt磷酸化在GJ给药20分钟后开始升高。基于这些结果以及GJ治疗后ed依赖性松弛迅速发生的事实，我们认为GJ的ed依赖性血管松弛作用主要是通过eNOS的钙依赖性激活和随后内皮细胞NO的产生来介导的。(C) 2012爱思唯尔公司版权所有。
Gomisin J (GJ) is a lignan contained in Schisandra chinensis (SC) which is a well-known medicinal herb for improvement of cardiovascular symptoms in Korean. Thus, the present study examined the vascular effects of GJ, and also determined the mechanisms involved. Exposure of rat thoracic aorta to GJ (1-30 mu g/ml) resulted in a concentration-dependent vasorelaxation, which was more prominent in the endothelium (ED)-intact aorta. ED-dependent relaxation induced by GJ was markedly attenuated by pretreatment with L-NAME, a nitric oxide synthase (NOS) inhibitor. In the intact endothelial cells of rat thoracic aorta. GJ also enhanced nitric oxide (NO) production. In studies using human coronary artery endothelial cells, GJ enhanced phosphorylation of endothelial NOS (eNOS) at Ser(1177) with increased cytosolic translocation of eNOS, and subsequently increased NO production. These effects of GJ were attenuated not only by calcium chelators including EGTA and BAPTA-AM, but also by LY294002, a PI3K/Akt inhibitor, indicating calcium- and PI3K/Akt-dependent activation of eNOS by GJ. Moreover, the levels of intracellular calcium were increased immediately after GJ administration, but Akt phosphorylation was started to increase at 20 min of GJ treatment. Based on these results with the facts that ED-dependent relaxation occurred rapidly after GJ treatment, it was suggested that the ED-dependent vasorelaxant effects of GJ were mediated mainly by calcium-dependent activation of eNOS with subsequent production of endothelial NO. (C) 2012 Elsevier Inc. All rights reserved.