The Research Of Cardioprotective Effect And Mechanism Of Echinacoside

Myocardial ischemia is one of the major causes of death throughout the world. Recently, several lines of investigation concerning Chinese traditional medicine in treating myocardial ischemia have converged because of their good effect and slight side effect. Echinacoside （ECH） is one of the major phenylethanoid glycoside （PhG） isolated from the various species especially including the stems of Cistanche tubulosa, which is a representative compound of PhG. Recently studies have indicated ECH had been shown to possess powerful ability of anti-oxidant and free radical scavenging properties. It has been evident that ECH had neuroprotective effects and prevent liver injuries. Besides, ECH has significant affects in anti-inflammatory, antitumor, antiaging, immunoregulation, improving learning memory and so on. However, ECH has never been used in cadiovascluar disease area, and this research should study the effect of ECH in improving the myocardial ischemia illustrated both in vivo and in vitro in these projects. Until now, there are many investigations detailing the important roles of the relationship between myocardial infraction and antoxidation, inflammation and apoptosis. The present study was to investigate its mechanism on myocardial ischemia with animal models, tissue and cardiomyocytes.1. The rat myocardial ischemia model （AMI） induced by ligating the left coronary artery descending （LAD） was used to observe the anti-myocardial ischemic effect of ECH, which has the significant effect on reducing infarct size and decreasing the level of LDH, CK-MB, SOD, and increase MDA in serum.2. ECH was studied on cultured myocyte subjected to H₂O₂, LPS, Na₂S₂O₄ and hypoxia respectively based on the index of cells viability, myocyte apoptosis rate, the content of ROS, the level of [Ca²⁺]_i, LDH and SOD. It was found that ECH （0.01, 0.1, 1, 10μM） had effect in MTT assay induced with H₂O₂ model in a dose manner. ECH （0.1, 1, 10μM） can significantly reduce the apoptotic myocytes population and ROS production in cardiomyocytes by flow cytometry assay induced by H₂O₂ and LPS model in a dose dependent manner. ECH （0.625, 3.125μM） could reduce the apoptotic myocytes population and ROS in cardiomyocytes by flow cytometry assay in hypoxia model. In addition, the effect could inhibit calcium overload of cardiomyocytes in H₂O₂ and hypoxia model significantly.3. ECH （30-300μM） exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of endothelial nitric oxide synthase （eNOS） inhibitor, N^w-nitro-L-arginine methyl ester （L-NNA, 100μM） , an unselective soluble guanylate cylcase （sGC） inhibitor, methylene blue （10μM）, and a selective sGC inhibitor, lH-[l,2,4]oxadiazolo[4,3-alpha]quinoxalin-l-one （ODQ, 1μM）. Atropine （10μM） could partially abolish the vosorelaxation. However, the cyclooxygenase inhibitor indomethacin （5μM） had no influence on the action. Echinacoside enhanced the cyclic guanosine monophosphate （cGMP） production in aortic rings contracted with PE. These results firstly indicate that echinacoside mediates endothelium-dependent vasodilator action in rat thoracic aortic rings through nitric oxide （NO）-cGMP pathway.In conclusion, the protective effects of ECH on myocardial ischemia have the relation with an advantage on improving heart function, lessening the oxidative and hypoxia injury, inhibiting calcium overload and cell apoptosis, anti-inflammation and vascular dilation.