The root of Astragalus membranaceus, known as "huang-qi", is one of the most widely used Chineseherbal medicines for the prevention and treatment of myocardial ischemic diseases. However, the mechanisms governing its therapeutic effects are largely unknown.AIMS OF THE STUDY:
The aims of the present study were to investigate the cardioprotective effect of the root extract of A. membranaceus (EAM) in myocardial ischemia and to explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and in vitro.MATERIALS AND METHODS:
The saponins in EAM were analyzed using HPLC. The tests for the cardioprotective effects of EAM and its mechanisms were performed in vivo and in vitro. In vivo, the rat model of persistent myocardial ischemia was produced by occlusion of the left anterior descending (LAD) coronary artery. In vitro, the cardiomyocyte model of oxidative stress was mimicked by the direct free radical donor, H2O2.RESULTS:
In vivo, the increased myocardial infarct size and the increased serum levels of lactate dehydrogenase (LDH), creatine kinase isoform MB (CK-MB), and cardiac troponin (cTnI) were significantly decreased by pre-treatment with EAM. Moreover, cardiac function, as assessed by±dP/dt, left ventricular developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP), was dramatically improved. An oxidative stress biomarker, malondialdehyde (MDA), was reduced, and the antioxidant enzyme superoxide dismutase (SOD) was induced. In vitro, H2O2-triggered myocardial cell death and cytoplasm Ca2+ overload were blocked by treatment with EAM. Furthermore, the KATP channel blocker (5-HD, glibenclamide) blocked the anti-apoptotic protective effect of EAM on cardiomyocytes injured by H2O2.CONCLUSIONS:
The cardioprotection of EAM was manifested as a protection of tissue structure and as a decrease in serum markers of ischemic injury. The mechanisms underlying the EAM-mediated protective effects may involve improving cardiac function, attenuating the oxidative injury via a decrease in MDA, a maintenance in SOD, and a reduction in free radical-induced myocardial cell injury. Additionally, EAM enhanced the myocardial cell viability via arresting the influx of Ca2+ to block cell death and opening mitochondrial KATP channels to reduce cell apoptosis.
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