Protection against myocardial ischemia reperfusion injury by liquiritin: involvement of autophagy restoration targeting PIK3CA.

The current therapy for myocardial infarction focuses on reestablishing blood flow in the coronary arteries to reduce the ischemic area, but the subsequent damage caused by reperfusion cannot be ignored. Liquiritin, a primary flavonoid compound found in the medicinal plant licorice, exhibits distinct pharmacological properties including neuroprotection, anti-inflammatory, antioxidant, and anti-apoptotic effects. However, further research on its role and mechanism in myocardial ischemia-reperfusion (I/R) injury is needed. The aim of this work was to elucidate the protection of liquiritin against myocardial I/R insult and whether liquiritin-mediated autophagy restoration was associated with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in vivo and in vitro. Liquiritin administration by oral gavage inhibited pathological injury of myocardial I/R injured rats, evidenced by improved cardiac function and reduced infarct size. Moreover, liquiritin restored excessive autophagy by promoting the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which was accompanied by PIK3CA upregulation. Mechanistically, silencing PIK3CA in rat H9c2 cardiomyoblasts diminished the beneficial effects against oxygen-glucose deprivation/reoxygenation (OGD/R) injury reflected by exacerbated apoptosis and dysregulated autophagy mediated by the classical PI3K/Akt/mTOR pathway. Liquiritin inhibited excessive autophagic flux via decreasing autophagosome-lysosome fusion, which was similar to the effect of the autophagy inhibitor chloroquine. Moreover, this phenomenon was enhanced when liquiritin and chloroquine were used in combination. Collectively, our work revealed that the protective effect of liquiritin against myocardial I/R injury may be attributed to its autophagy restoration mediated by PIK3CA.