Crataegus special extract WS® 1442 induces an endothelium-dependent, NO-mediated vasorelaxation via eNOS-phosphorylation at serine 1177
Crataegus special extract WS® 1442 induces an endothelium-dependent, NO-mediated vasorelaxation via eNOS-phosphorylation at serine 1177
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DOI：
10.1007/s10557-006-8723-7
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发表时间：
2006-06-01
影响因子：
3.4
通讯作者：
Schwinger, Robert H. G.
中科院分区：
文献类型：
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作者：
Brixius, Klara;Willms, Sonja;Schwinger, Robert H. G.
目的研究山楂花叶提取物WS(R)1442对大鼠主动脉和人(冠脉搭桥术)患者的血管舒张性的影响。此外，我们还研究了WS(R)1442的三个组分(组分A：亲脂性，含黄酮类和低聚原花青素(OPC)，组分B：亲水性，含黄酮类和低分子量OPC，组分C：亲水性，基本上不含黄酮类化合物，富含高相对分子质量OPC)。结果WS(R)1442对10mU苯肾上腺素预收缩的血管环具有浓度依赖性的血管扩张作用(IC50)：大鼠：15.1+/-0.6mU g/ml(n=7)，人：19.3+/-3.4微克/毫升(n=6)。100 mU WS(R)1442的最大舒血管效应是罂粟碱0.1 mM的75.0±5.7%(大鼠)和79.2±5.8%(人)。如果实验是在L-硝基精氨酸甲酯(10mU M，eNOS抑制)存在的情况下进行的，或者在机械破坏内皮后进行，则在WS(R)1442的存在下没有观察到血管松弛。WS(R)1442的血管松弛特性是由组分C介导的。用二氨基荧光素测定，WS(R)1442可诱导人冠状动脉内皮细胞释放NO。WS(R)1442诱导的eNOS激活是由于丝氨酸1177的磷酸化。应用WS(R)1442后，未观察到丝氨酸114或苏氨酸495位eNOS易位或磷酸化。结论WS(R)1442通过丝氨酸1177位eNOS磷酸化诱导内皮依赖的NO介导的血管松弛。
Purpose This study investigates the influence of WS (R) 1442, a special extract of Crataegus leaves with flowers, on the relaxation of rat aorta and human mammarian artery (coronary bypass patients).Methods Experiments were performed in the presence and absence (mechanical disruption) of endothelium. In addition, we investigated three fractions of WS (R) 1442 (fraction A: lipophilic, containing flavonoids and oligomeric procyanidins (OPC), fraction B: hydrophilic, containing flavonoids and low molecular weight OPC, fraction C: hydrophilic, essentially flavonoid-free and rich in high molecular weight OPC).Results WS (R) 1442 induced a concentration-dependent vasodilation in isolated vessel rings that had been precontracted by 10 mu M phenylephrine (concentration for halfmaximal relaxation (IC50): rat: 15.1 +/- 0.6 mu g/ml (n = 7), human: 19.3 +/- 3.4 mu g/ml (n = 6)). The maximal vasorelaxation induced after application of 100 mu g of WS (R) 1442 was 75.0 +/- 5.7% (rat) and 79.2 +/- 5.8% (human) of the papaverine (0.1 mM)-induced vasodilation. If the experiments were performed in the presence of L-nitroarginine methylester (10 mu M, eNOS-inhibition) or after mechanical disruption of the endothelium, no vasorelaxation was observed in the presence of WS (R) 1442. The vasorelaxant properties of WS (R) 1442 were mediated by fraction C. WS (R) 1442 induced an NO-liberation from human coronary artery endothelial cells as measured by diaminofluorescein. WS (R) 1442 induced eNOS-activation was due to a phosphorylation at serine 1177. No eNOS-translocation or phosphorylation at serine 114 or threonine 495 was observed after application of WS (R) 1442.Conclusions It is concluded that WS (R) 1442, induces an endothelium-dependent, NO-mediated vasorelaxation via eNOS phosphorylation at serine 1177.