Dear Editor PLOS ONEThe freeze-dried extracts of Salvia coccinea Juss. Ex Murray attenuate myocardial ischemia reperfusion injury in a global ischemia Rat model

Abstract

BackgroundIschemia reperfusion injury is the leading cause of myocardial cell death in Ischemic Heart Disease. Thus intensive research efforts are geared at discovering pharmacological approaches that prevent it. Over twenty species from the genus Salvia are widely applied in traditional Chinese medicine in the management of heart diseases with Salvia miltiorrhiza (Danshen) being a canonical example. Our study aimed to investigate the cardio-protective effects of the freeze-dried extracts of salvia coccinea against ischemia reperfusion injury in a rodent in-vitro model of global ischemia.\n\nMethodsForty two (42) Sprague Dawley rats were randomly assigned into five groups: positive control (Glucosamine 1000mg/kg), negative control group (Krebs Henseleit buffer), low dose test (50 mg/100ml), medium dose test (100 mg/100ml), and high dose test (200 mg/100ml).\n\nThe cardio-protective effects of the different treatments were evaluated in a global ischemia model using isolated rat hearts mounted on a Langendorff system.\n\nNaloxone 2.2 mol/L ( opioid receptor blocker), and theophylline 1000 mol/L (non-specific adenosine receptor blocker) were co-administered with 50 mg of S.coccinea in the mechanism of action experiments.\n\nThe following indices of cardiac function were recorded pre- and post-ischemia: left ventricular developed pressure (LVDP), heart rate, and maximum rate of contraction and relaxation. All data were expressed as Mean {+/-} Standard Error of Mean and analyzed using one-way ANOVA and Tukey post-hoc tests. Significance was set at p < 0.05.\n\nResultsThe freeze-dried extracts of S. coccinea had significant effects on post-ischemic contractile function recovery in the early [51.4 {+/-} 9.7% (low dose test) vs. 14.9 {+/-} 3.3% (medium dose test) vs. 12.7 {+/-} 2.6% (high dose test) vs. 13.7 {+/-} 5.7% (negative control): p<0.05] and late [38.6 {+/-} 8.9% (low dose test) vs. 22.0{+/-} 7.1% (medium dose test) vs. 14.6 {+/-} 5.8 (high dose test) vs. 12.5 {+/-} 4.2% (negative control): p< 0.05]. Reperfusion phases with the highest LVDP recovery were observed at the 50 mg dosage level.\n\nThe freeze-dried extracts of S. coccinea had significant negative chronotropic effects on heart rate [234.0 {+/-} 2.4 beats/min to 90.0 {+/-} 7.0 beats/min, 50 mg vs. 102.0 {+/-} 13.9 beats/min to 135.0 {+/-} 25.9 beats/min, control P<0.05].\n\nThe cardioprotective effects of S. coccinea displayed an inverted U-shaped dose-response curve with low dose stimulation and high dose inhibition.\n\nNaloxone completely abolished the LVDP recovery afforded by the freeze-dried extracts of S. coccinea at the 50 mg dosage level while adenosine only partly abolished the LVDP recovery (9.5 {+/-} 3.2% (naloxone) vs. 15.5 {+/-} 5.8% (adenosine): P>0.05).\n\nConclusionThe freeze-dried extracts of S. coccinea possessed significant cardioprotective effects which appear to be mediated by activation of the opioidergic pathway in the heart.