Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary artery endothelial cell damage by regulating mitochondria.

Hypoxia/reoxygenation (H/R) is one of the main causes of coronary artery disease (CAD), which is primarily induced by damage to coronary artery endothelial cells (CAECs). Glycyrrhizic acid (GA) is a natural and abundant pentacyclic triterpenoid glycoside of the licorice root extract, and it has been reported to elicit protective effects against hypoxia, inflammation and apoptosis in ischemic myocardium; therefore, GA may serve as a promising therapeutic agent for ischemia-associated CAD. In the present study, the protective effects of GA against H/R-induced injury in CAECs were investigated. Treatment with GA during H/R maintained cell viability and decreased H/R-induced cell apoptosis in human CAECs. In addition, H/R-mediated induction of intracellular and mitochondrial reactive oxygen species (ROS) was significantly decreased by GA exposure. Similar to ROS scavengers, GA treatment not only exhibited protective effects, but also maintained the mitochondrial membrane potential after H/R and inhibited H/R-induced mitochondrial dysfunction, including deficits in ATP synthesis, mitochondrial DNA copy number and mitochondrial transcriptional activity. Furthermore, GA decreased autophagy/mitophagy, and its protective effect against H/R was abolished by autophagy promotion. Collectively, the results suggested that GA exhibited protective effects against H/R-induced CAEC injury by decreasing ROS accumulation and maintaining mitochondrial homeostasis. Further investigation into the precise mechanisms underlying the decrease in ROS accumulation induced by GA is required.