J Korean Med Sci.  2012 May;27(5):572-575. 10.3346/jkms.2012.27.5.572.

Protective Effect of Sauchinone Against Regional Myocardial Ischemia/Reperfusion Injury: Inhibition of p38 MAPK and JNK Death Signaling Pathways

• Kim SJ
• Jeong CW
• Bae HB
• Kwak SH
• Son JK
• Seo CS
• Lee HJ
• Lee J
• Yoo KY

• KMID: 1372805
• DOI: http://doi.org/10.3346/jkms.2012.27.5.572

Abstract

Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3beta was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% +/- 5.3% in the sauchinone group vs 44.4% +/- 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3beta was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.

Keyword

Sauchinone; Cardioprotection; Ischemia/reperfusion Injury; Cell Death Signaling Pathway; Reperfusion Injury Salvage Kinase Pathway

MeSH Terms

Animals
Benzopyrans/*pharmacology
Dioxoles/*pharmacology
Glycogen Synthase Kinase 3/metabolism
JNK Mitogen-Activated Protein Kinases/*metabolism
Mitogen-Activated Protein Kinase 1/metabolism
Mitogen-Activated Protein Kinase 3/metabolism
Myocardial Reperfusion Injury/*metabolism/pathology/prevention & control
Phosphorylation
Protective Agents/*pharmacology
Rats
Signal Transduction/*drug effects
p38 Mitogen-Activated Protein Kinases/*metabolism

Figure

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  Fig. 1 Experimental protocol. Sauchinone (10 mg/kg) and dimethyl sulfoxide (DMSO) were administered intraperitoneally 30 min before ischemia.

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  Fig. 2 Effects of sauchinone on the infarct size. All rats were subjected to 20 min regional ischemia followed by 2 hr of reperfusion. The infarct size is expressed as a percentage of area at risk. Sauchinone reduced infarct size, while DMSO alone was without effects. Values are mean ± SD. *P < 0.05 vs control.

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  Fig. 3 Effects of sauchinone on the expression of total and phosphorylated p38 (A), JNK (B), ERK1/2 (C), Akt (D), and GSK-3β (E). Sauchinone (10 mg/kg) attenuated the phosphorylation of p38 and JNK, while it did not affect that of ERK1/2, Akt and GSK-3β. The expression of total p38, JNK, ERK1/2, Akt, or GSK-3β was not altered by sauchinone. Upper panels show representative immunoblots, and lower panels show densitometric data. Sham group was without I/R. Values are mean ± SD. *P < 0.05 vs sham; †P < 0.05 vs control.

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