Abstract P19: Natural Antioxidant-Isoliquiritigenin Protects Heart against Ischemia-Reperfusion Injury via Activation of Cardioprotective Signaling Pathways
Background: Isoliquiritigenin (ISL), a simple chalcone-type flavonoid, which is derived from licorice compounds and mainly present in foods, beverages and tobacco. ISL is a natural antioxidant. There is amount of evidence that reactive oxygen species (ROS) is a critical factor involved in cardiac damage and apoptosis associated signaling pathways during ischemia/reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via scavenging ROS and regulating cardioprotective signaling pathways.
Methods and Results: To test this hypothesis, Langendorf ex vivo perfused FVB/NJ mouse hearts were performed ischemia (15 min) and reperfusion (30 min). The results demonstrated 72±8% recovery of the post-ischemic left ventricular contractility. Intriguingly, ISL (100 μM) treatment prior to reperfusion significantly improved the post-ischemic recovery of left ventricular contractility to 89±10% (p<0.05). Moreover, the IonOptix System measurement data showed that ISL treatment markedly ameliorated the hypoxic contractile dysfunction of isolated cardiomyocytes. The immunoblotting data revealed that ISL (100 μM) stimulated cardiac AMP-activated protein kinase (AMPK) and STAT3 signaling pathways, both of which are important cardioprotective signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL dramatically reduced the cardiac ROS level during ischemia/reperfusion. ISL also inhibited the reduction of mitochondrial membrane potential (ΔΨ) of cardiomyocytes caused by hypoxia and stimulated cardiac glucose uptake determined by 2-deoxy-D-[1-3H]glucose accumulation. Furthermore, ISL treatment significantly inhibited activation of cardiac c-Jun N-terminal protein kinase (JNK) and secretion of inflammatory factors, such as TNFαand IL-6, in the circulation during ischemia/reperfusion.
Conclusions: ISL protects heart against myocardial injury mediated by ischemia/reperfusion. The mechanisms of cardioprotection effect of ISL might be due to the reduction of ROS level and regulation of substrate metabolism & inflammatory response during ischemia/reperfusion. ISL is a potential small molecule for treatment of ischemic heart diseases in the future.
This research has received full or partial funding support from the American Heart Association, National Center.