Berberine Attenuates Ischemia-Reperfusion Injury Via Regulation of Adenosine-5'-monophosphate Kinase Activity in Both Non-ischemic and Ischemic Areas of the Rat Heart

Berberine exhibits numerous pharmacological effects, but the mechanism for its protective effects against ischemia-reperfusion cardiac injury is unknown. Male Wistar rats were treated with berberine (100 mg/Kg/day, ig) for 14 days and controls treated with water. Hearts were isolated in vitro and perfused in the Langendorff mode and subjected to 30 min of global ischemia followed by 30 min of reperfusion and hemodynamic data examined. In a separate set of experiments, hearts were subjected in vivo to left anterior descending coronary artery ligation for 30 min followed by 120 min reperfusion and hemodynamic data, type and duration of arrhythmias, and myocardial infarct size determined. AMP-activated protein kinase (AMPK) level, ADP/ATP and AMP/ATP ratios were examined in non-ischemic areas and risk areas of the heart. Subsequent to ischemia-reperfusion injury, left ventricular developed pressure, left ventricular end diastolic pressure and maximum rate of intraventricular pressure contractility and relaxation were significantly improved in the berberine treatment groups compared to controls. Berberine treatment decreased infarct size and diminished the duration and incidence of arrhythmias compared to controls. Berberine treatment significantly decreased AMPK protein concentration, and the ratio of ADP/ATP and AMP/ATP in the myocardial risk areas. In contrast, berberine treatment significantly increased AMPK protein concentration, and the ratio of ADP/ATP and AMP/ATP in the non-ischemia areas compared to controls. These findings suggest that berberine may exert its cardioprotective effect on ischemia-reperfusion injury via regulation of AMPK activity in both non-ischemic areas and risk areas of the heart.