Nobiletin suppresses oxidative stress and apoptosis in H9c2 cardiomyocytes following hypoxia/reoxygenation injury.

Nobiletin (3′,4’,5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found in Citrus fruits, was reported to exhibit protective activity against ischemia/reperfusion (I/R). However, the role of nobiletin in myocardial I/R injury remains unclear. This study was designed to examine the cardioprotective effect of nobiletin from myocardial hypoxia/reoxygenation (H/R) injury in vitro, and to explore the potential molecular mechanisms. Our results showed that nobiletin improved cell viability in H9c2 cells after H/R treatment. In addition, nobiletin significantly inhibited the production of reactive oxygen species and malondialdehyde (MDA), cell apoptosis, as well as suppressed the levels of pro-inflammatory factors in H/R-stimulated H9c2 cells. Furthermore, we observed that pretreatment with nobiletin significantly activated the Akt/GSK-3β signaling pathway in H/R-stimulated H9c2 cells. Taken together, these findings demonstrated that nobiletin attenuates myocardial I/R injury via the activation of Akt/GSK-3β pathway in H9c2 cardiomyocytes. Thus, nobiletin may be regarded as a promising drug for the prevention of myocardial I/R injury and ischemic heart disease.