Curcumin attenuates hypoxia/reoxygenation­induced cardiomyocyte injury by downregulating Notch signaling.

Recovery of the blood supply is the most effective treatment against ischemic heart disease; however, it is also a major cause of myocardial ischemia/reperfusion injury in clinical therapy. Curcumin has been reported to possess beneficial effects against hypoxia/reoxygenation (H/R)­induced cardiomyocyte injury by regulating cell proliferation, apoptosis and antioxidant enzyme activity. The aim of the present study was to investigate the molecular mechanisms underlying the effects of curcumin on H/R­injured cardiomyocytes. H9C2 cardiomyocytes were pretreated with curcumin, and then cultured under H/R conditions. The viability of H9C2 cells was measured using a Cell Counting kit­8 assay, and the levels of intracellular lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to assess cell injury. Levels of reactive oxygen species (ROS) and apoptosis were evaluated by flow cytometry. The expression levels of Notch intracellular domain (NICD) and numerous downstream genes were analyzed via reverse transcription­quantitative polymerase chain reaction and western blotting. The results revealed that curcumin protected H9C2 cells against H/R­induced injury, reversing the H/R­induced increases in LDH and MDA levels, and decreases in SOD levels. ROS levels in H/R­induced cells were also significantly downregulated by curcumin treatment (P<0.01), and the apoptotic rate was significantly decreased from 15.13% in the H/R group to 7.7% in the H/R + curcumin group (P<0.01). The expression levels of NICD, hairy and enhancer of split (Hes)­1, Hes­5 and hairy/enhancer­of­split related with YRPW motif protein 1 (Hey­1) were significantly decreased in H/R­treated cells following curcumin treatment. Treatment with Jagged1 attenuated the effects of curcumin on cell viability, ROS levels and apoptosis; the Notch pathway was also reactivated. The present study indicated that there was a role for the Notch pathway in the protective effects of curcumin against H/R­induced cardiomyocyte injury, suggesting that downregulation of the Notch pathway may alleviate H/R­induced injury in H9C2 cells.