orientin and Myocardial-Ischemia

In this study, we provide new evidence that orientin from bamboo leaves (Phyllostachys nigra) protect H9c2 cardiomyocytes against ischemia/reperfusion (I/R) injury through the mitochondrial apoptotic pathway. A previous work has identified that orientin could protect myocardium against ischemia/reperfusion injury. Mitochondria are both critical determinants of cardioprotection and crucial targets of cardioprotective signaling. Their role during reperfusion is conspicuously critical because the conditions promote apoptosis through the mitochondrial pathway and necrosis though irreversible damage to mitochondria, which is in association with mitochondrial permeability transition (MPT). After myocardial ischemia, opening of the mPTP is a critical determinant of cell death. The relationship of orientin and mPTP in mediating reperfusion-induced cardiomyocytes injury is still elusive. Here, our results indicate that the protective effect of orientin in H9c2 cells subjected to I/R injury is associated with depression of the mPTP opening, resultant mitochondrial dysfunction, and apoptosis. Further investigation of cellular mechanisms revealed that these effects were associated with inhibition of reactive oxygen species (ROS) generation, repolarization of mitochondrial membrane potential (Δψ(m)), suppression of mitochondrial cytochrome C release, enhancement of the Bcl-2 level, and inhibition of Bax and Smac/DIABLO levels. Furthermore, these beneficial effects of orientin were blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, and orientin could enhance Akt phosphorylation. In summary, we demonstrate that orientin protects H9c2 cardiomytocytes against I/R-induced apoptosis by modulating the mPTP opening, and this role of orientin may involve the PI3K/Akt signaling pathway.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Carrier Proteins; Cell Line; Cytochromes c; Cytosol; Flavonoids; Glucosides; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Mitochondrial Proteins; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocytes, Cardiac; Permeability; Phosphatidylinositol 3-Kinase; Phosphorylation; Protective Agents; Protein Transport; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Signal Transduction

To study the protective effects of orientin against myocardial ischemia and hypoxia in rats.. The protective effect of orientin against myocardial ischemia and hypoxia was observed in mice by recording their survival time under closed normobaric hypoxia and time of cardiac electric disappearance due to trachea clamping, in rabbits by evaluating arachidonic acid (AA)-induced blood platelet aggregation, in guinea pigs by measuring the coronal flow in the isolated heart and in SD rats with myocardial ischemia induced by pituitrin injection.. Orientin (1, 2, 4 mg/kg) significantly prolonged the survival time of mice under closed normobaric hypoxia and the gasping duration induced by decapitation. Orientin at concentrations of 3, 10, and 30 micromol/L also inhibited AA-induced blood platelet aggregation in rabbits and increased coronal flow in the isolated heart of guinea pigs. At 0.75, 1.5, and 3.0 mg/kg, orientin significantly antagonized pituitrin-induced ECG changes.. Orientin may offer protection against myocardial ischemia and hypoxia in animal models in dose-dependent fashions.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; Female; Flavonoids; Glucosides; Guinea Pigs; Hypoxia; Male; Mice; Myocardial Ischemia; Platelet Aggregation; Rabbits; Rats; Survival Rate