Life Sciences

Volume 122, 1 February 2015, Pages 15–25

Luteolin inhibits ROS-activated MAPK pathway in myocardial ischemia/reperfusion injury

• Dongsheng Yu^a,
• Mengwen Li^a,
• Youqing Tian^b,
• Jun Liu^a,
• Jing Shang^{a, c, ,}

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doi:10.1016/j.lfs.2014.11.014

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Abstract

Aims

Luteolin is a falconoid compound that has an antioxidant effect, but its contribution to ROS-activated MAPK pathways in ischemia/reperfusion injury is seldom reported. Here, we have confirmed that it exhibits an antioxidant effect in myocardial ischemia/reperfusion injury (MIRI) by inhibiting ROS-activated MAPK pathways.

Main methods

We exposed rat hearts into the left anterior descending coronary artery (LAD) ligation for 30 min followed by 1 h of reperfusion. Observations were carried out using electrocardiography; detection of hemodynamic parameters; and testing levels of lactate dehydrogenase (LDH), creatine kinase (CK), total superoxide dismutase (T-SOD), and malondialdehyde (MDA). Mitogen-activated protein kinase (MAPK) pathway was measured by western blot and transmission electron microscopy was applied to observe the myocardial ultrastructure. Rat H9c2 cell in 95% N₂ and 5% CO₂ stimulated the MIRI. Oxidation system mRNA levels were measured by real-time PCR; mitochondrial membrane potential and apoptosis were measured by confocal microscopy and flow cytometry; western blot analysis was used to assay caspase-3, -8, and -9 and MAPK pathway protein expression; the MAPK pathway was inhibited using SB203580 (p38 MAPK inhibitor) and SP600125 (c-Jun NH₂-terminal kinase inhibitor) before H9c2 cells were exposed to hypoxia/reoxygenation injury to show the modulation of the changes in ROS generation, cell viability and apoptosis.

Key findings

In vivo, luteolin can ameliorate the impaired mitochondrial morphology, regulating the MAPK pathway to protect MIRI. In vitro, luteolin can affect the oxidation system, mitochondrial membrane potential and MAPK pathway to anti-apoptosis.

Significance

These results reveal a ROS–MAPK mediated mechanism and mitochondrial pathway through which luteolin can protect myocardial ischemia/reperfusion injury.

Keywords

• Luteolin;
• Myocardial ischemia/reperfusion injury;
• Reactive oxygen species;
• MAPK;
• Mitochondrial;
• Apoptosis

Corresponding author at: Center for Drug Screening & State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Tel.: + 86 25 83271057; fax: + 86 25 83271142.

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