Luteolin inhibits apoptosis and improves cardiomyocyte contractile function through the PI3K/Akt pathway in simulated ischemia/reperfusion.

Abstract

Luteolin, a naturally occurring polyphenol flavonoid, has demonstrated to exert myocardial protection effects. However, the mechanisms have not been fully elucidated. In the present study, we investigated whether luteolin pretreatment was associated with cardioprotection in a rat ischemia/reperfusion (I/R) model. Luteolin significantly not only restored contractility of the left ventricle, but also reduced the infarct size and lactate dehydrogenase leakage during I/R. In addition, luteolin pretreatment significantly improved cardiomyocyte shortening amplitude, decreased the apoptotic rate, upregulated Bcl-2 expression, downregulated Bax expression and raised the Bcl-2/Bax ratio under a simulated ischemia/reperfusion (SI/R) condition. Moreover, luteolin pretreatment increased protein kinase B (Akt) phosphorylation, phospholamban phosphorylation and the expression of sarcoplasmic reticulum calcium ATPase following SI/R. The phosphoinositide 3-kinase (PI3K)/Akt pathway is one of the most important intracellular survival signal pathways. To determine whether luteolin-induced cardioprotection was mediated by the PI3K/Akt pathway, we utilized the PI3K inhibitor LY294002. Inhibition of Akt activity markedly abolished luteolin-induced positive contraction and inhibition of apoptosis in SI/R cardiomyocytes. These results showed that luteolin inhibits apoptosis and improves cardiomyocyte contractile function at least partly through the PI3K/Akt pathway in SI/R.

• Authors: Fang Fang, Dongye Li, Huanjun Pan, Dan Chen, Lingling Qi, Ruiqu Zhang, Hong Sun
• Journal: Pharmacology (Pharmacology) Vol. 88 Issue 3-4 Pg. 149-58 ( 2011) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 21934351 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Calcium-Binding Proteins
• Cardiotonic Agents
• Chromones
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• phospholamban
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• L-Lactate Dehydrogenase
• Proto-Oncogene Proteins c-akt
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Luteolin

Topics

• Animals
• Apoptosis (drug effects)
• Calcium-Binding Proteins (biosynthesis)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Chromones (pharmacology)
• Disease Models, Animal
• Heart (drug effects, physiopathology)
• L-Lactate Dehydrogenase (metabolism)
• Luteolin (pharmacology, therapeutic use)
• Male
• Morpholines (pharmacology)
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Myocytes, Cardiac (drug effects, metabolism, physiology)
• Phosphatidylinositol 3-Kinases (physiology)
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, physiology)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (biosynthesis)
• bcl-2-Associated X Protein (metabolism)