Cardioprotective effects of oleanolic acid under hyperglycemic conditions

We previously found that hyperglycemia elicits oxidative stress leading to apoptosis and decreased cardiac function. Here we tested if oleanolic acid (OA) (from Syzigium aromaticum ) possesses antioxidant properties and is able to blunt hyperglycemia‐mediated effects. We employed 2 experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hrs vs. matched controls (5 mM glucose); where after cells were treated with two OA doses (20 and 50 μM) for 6 and 24 hrs, respectively. Oxidative stress was assessed by immunofluorescence microscopy and flow cytometry (DCF staining), and apoptosis by caspase activity assays; and 2) Isolated rat hearts were perfused with Krebs‐Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion. To ascertain whether OA acts as a cardioprotective agent, we administered a 100 μM dose at the beginning of reperfusion vs. controls. Our in vitro data demonstrate that OA blunted hyperglycemia‐induced oxidative stress and apoptosis. OA treatment also markedly improved functional recovery of hearts perfused under hyperglycemic conditions. This study shows that oleanolic acid displays antioxidant and anti‐apoptotic properties that contribute to improved functional recovery of ischemic hearts under hyperglycemic conditions. Funding: SA NRF, MRC, Stellenbosch University.