title: Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia.
abstract: BACKGROUND
  The root of Astragalus membranaceus, known as "huang-qi", is one of the most widely used Chinese herbal medicines for the prevention and treatment of myocardial ischemic diseases. However, the mechanisms governing its therapeutic effects are largely unknown.
  
  
  OBJECTIVE
  The aims of the present study were to investigate the cardioprotective effect of the root extract of Astragalu membranaceus (EAM) in myocardial ischemia and to explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and in vitro.
  
  
  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 Ca(2+) 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 Ca(2+) to block cell death and opening mitochondrial KATP channels to reduce cell apoptosis.
authors: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors: Xu
authors: X
authors: Ma
authors: Ke
authors: K
authors: Zhang
authors: Haixia
authors: H
authors: Li
authors: Shuyan
authors: S
authors: Han
authors: Zhizhong
authors: Z
authors: Ma
authors: Pengfei
authors: P
authors: Tu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D027885:Astragalus propinquus / Q000737:chemistry*; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000627:therapeutic use*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; D002118:Calcium
keywords: Antioxidant; Apoptosis.; Astragalus membranaceus; Cardioprotection; KATP channel; Myocardial ischemia