Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury

Swaminathan, J.K.; Khan, M.; Mohan, I.K.; Selvendiran, K.; Niranjali Devaraj, S.; Rivera, B.K.; Kuppusamy, P.

doi:10.1016/j.phymed.2010.01.009

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Volume 17, Issue 10 , Pages 744-752, August 2010

Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury

J.K. Swaminathan
- Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, 420 West 12th Ave, Room 114, Columbus, OH 43210, USA
- Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
M. Khan
- Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, 420 West 12th Ave, Room 114, Columbus, OH 43210, USA
I.K. Mohan
- Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, 420 West 12th Ave, Room 114, Columbus, OH 43210, USA
K. Selvendiran
- Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, 420 West 12th Ave, Room 114, Columbus, OH 43210, USA
S. Niranjali Devaraj
- Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
B.K. Rivera
- Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, 420 West 12th Ave, Room 114, Columbus, OH 43210, USA
P. Kuppusamy
- Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, 420 West 12th Ave, Room 114, Columbus, OH 43210, USA
- Corresponding author. Tel.: +6142928998; fax: +6142928454.

published online 19 February 2010.

Abstract

The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30min of global ischemia followed by 45min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1mg/ml/min for 10min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1α that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection.

Keywords: Oxidative stress, Infarction, Ischemia-reperfusion injury, Rat heart, Crataegus oxycantha, Apoptosis

Abbreviations: COC, Crataegus oxycantha, I/R, Ischemia/reperfusion, OPC, Oligomeric proanthocyanidin, ROS, Reactive oxygen species, LVDP, Left ventricular developed pressure, CF, Coronary flow, HR, Heart rate, RPP, Rate pressure product, LDH, Lactate dehydrogenase, CK, Creatine kinase, TTC, Triphenyltetrazolium chloride