Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury.
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-1alpha 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.
Swaminathan
J K
JK
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.
Khan
M
M
Mohan
I K
IK
Selvendiran
K
K
Niranjali Devaraj
S
S
Rivera
B K
BK
Kuppusamy
P
P
D000818:Animals; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D027825:Crataegus / Q000737:chemistry*; D003402:Creatine Kinase / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D002316:Cardiotonic Agents; D010936:Plant Extracts; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase