Cardiovascular PharmacologyLuteolin improves contractile function and attenuates apoptosis following ischemia-reperfusion in adult rat cardiomyocytes

Luteolin occurs in a variety of plants and possesses antioxidant and anti-inflammatory properties. However, its role in protection against ischemia-reperfusion injury in Sprague-Dawley rats has not been elucidated. In the present study, we tested the contractile function of left ventricular cardiomyocytes with different concentrations of luteolin: 0.5, 1.5, 2.5 and 5.0 μg/ml after simulated. We investigated the direct effect of luteolin against necrosis and apoptosis following ischemia-reperfusion in cardiomyocytes. We further observed the function of isolated hearts subjected to ischemia-reperfusion with or without 10.0 μg/ml luteolin pretreatment. Following 24 h incubation with or without luteolin, adult rat cardiomyocytes were subjected to 3 h of ischemia followed by 2 h of reperfusion for contractile function and necrosis (trypan blue exclusion and lactate dehydrogenase release) or 18 h of reperfusion for apoptosis studies. The cardiomyocyte shortening amplitude depended on different concentrations of luteolin, increasing significantly at 2.5 μg/ml luteolin (P < 0.01). Necrosis and apoptosis were reduced by luteolin at 2.5 μg/ml. In addition, the expression of Bcl-2 was upregulated by luteolin and the ratio of Bax to Bcl-2 was decreased. Luteolin inhibited the activation of Caspase3 after ischemia-reperfusion in cardiomyocytes. Furthermore, luteolin at 10.0 μg/ml improved ischemia-reperfusion induced myocardial function, by improving heart rate, + dp/dtmax and − dp/dtmax, and also limiting the decline of left ventricular systolic pressure (LVSP) and elevation of left ventricular end-diastolic pressure (LVEDP) to some extent. Our results demonstrated that luteolin prevents ischemia-reperfusion injury by reducing necrosis and apoptosis in rat cardiomyocytes.