Korean Circ J.  2008 Jul;38(7):353-359. 10.4070/kcj.2008.38.7.353.

The Protective Effect of Curcumin on Myocardial Ischemia-Reperfusion Injury

• Kim YS
• Park HJ
• Joo SY
• Hong MH
• Kim KH
• Hong YJ
• Kim JH
• Park HW
• Jeong MH
• Cho JG
• Park JC
• Ahn Y

• KMID: 2225768
• DOI: http://doi.org/10.4070/kcj.2008.38.7.353

Abstract

BACKGROUND AND OBJECTIVES: Myocardial ischemia-reperfusion (I/R) injury is one of the major causes of cardiac mortality. Curcumin, an active component extracted from turmeric in curry, inhibits inflammatory responses. This study was designed to investigate whether curcumin can exert beneficial effects on myocardial I/R injury.
MATERIALS AND METHODS
Sprague-Dawley male rats received a normal diet or a curcumin diet (80 mg/kg/d) for one week, and I/R injury was induced by ligating the left anterior descending artery (LAD) for 30 min followed by release. After 24 hours, the myocardium was extracted to evaluate the myeloperoxidase (MPO) activity and the vascular cellular adhesion molecule (VCAM)-1 protein level. The apoptotic cardiomyocytes and neutrophils were counted and quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining at 14 days after I/R.
RESULTS
In the infarcted myocardium of the curcumin-fed rats, the MPO activity (32.9+/-2.2% of the control, p=0.001) and the VCAM-1 protein (28.7+/-2.9% of control, p=0.001) level were significantly attenuated. The number of neutrophils was lower in the curcumin-fed rats (57+/-12% of the control, p=0.024). A reduction of the apoptotic cardiomyocytes was also observed in the curcumin-fed I/R rats (36+/-9.2% of the control, p=0.032).
CONCLUSION
The cardioprotective effects of curcumin on an I/R injury rat model could include anti-inflammation activities and inhibition of apoptosis that occurred in the cardiomyocytes. Our findings suggest that curcumin has a positive contribution as a dietary supplement for the prevention of heart disease.

Keyword

Curcumin; Ischemia-reperfusion injury; Inflammation; Apoptosis

MeSH Terms

Animals
Apoptosis
Arteries
Curcuma
Curcumin
Diet
Dietary Supplements
Heart Diseases
Humans
Inflammation
Male
Myocardium
Myocytes, Cardiac
Neutrophils
Peroxidase
Rats
Reperfusion Injury
Vascular Cell Adhesion Molecule-1
Curcumin
Peroxidase
Vascular Cell Adhesion Molecule-1

Figure

• 

  Fig. 1 Myeloperoxidase (MPO) activity and malondialdehyde (MDA) formation were assessed at 24 hours after inducing I/R, and the neutrophils were counted at 2 weeks after inducing I/R. A: the MPO activity in the infarct region was significantly decreased in the curcumin+I/R group compared with that in the control group. B: the number of infiltrated neutrophils in the infarct region was reduced in the curcumin+I/R group compared with the I/R group. C: the level of MDA in the infarct region was lower in the curcumin+I/R group. *p<0.05, values are means±S.Ds. NI: non-infarct, I: infarct, I/R: ischemia-reperfusion, Cur: curcumin.

• 

  Fig. 2 The expression of VCAM-1 and the activation of NF-κB were examined. A: the level of VCAM-1 protein in the heart tissue 24 h after I/R injury was determined by Western blotting. The expression of VCAM-1 protein in the infarct region was attenuated in the curcumin+I/R group. B: the activation of NF-κB 24 h after I/R injury was determined by Western blotting by using NF-κB p65 subunit antibody. Activated NF-κB p65 was translocated to the nuclear fraction from the cytosol fraction. In the I/R group, nuclear factor (NF)-κB p65 was increased in the nuclear fraction (nuc) of the infarct region, while this was reduced in the curcumin+I/R group. C: immunocytochemistry was performed on the rat neonatal cardiomyocytes. Nuclear factor (NF)-κB p65 was stained with Alexa488 (green) and the nucleus was stained with DAPI (blue). In the normal cardiomyocytes, NF-κB p65 was located in the cytosol in a diffuse manner. NF-κB p65 was translocated to the nucleus in the hypoxia/reoxygenated cardiomyocytes, where it abided in the perinuclear cytosol in the curcumin+hypoxia/reoxygenated cardiomyocytes. NI: non-infarct, I: infarct, I/R: ischemia-reperfusion, Cur: curcumin, VCAM: vascular cellular adhesion molecule, DAPI: 4'-6-diamidino-2-phenylindole.

• 

  Fig. 3 M-mode echocardiography at 2 weeks after I/R. Fractional shortening (%) was significantly preserved in the curcumin+I/R group compared with that in the control group. *p<0.05, values are means±S.Ds. I/R: ischemia-reperfusion, Cur: curcumin.

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  Fig. 4 Curcumin reduced the cardiac fibrosis and a poptosis. A: cardiac fibrosis was determined by Masson's trichrome staining. Fibrosis in the infarct region was significantly decreased in the curcumin+I/R group. B: apoptosis was assessed by TUNEL staining. C: the number of apoptotic cells (brown stained) in the infarct region was lower in the curcumin+I/R group than that in the I/R group (original magnification, 200×). *p<0.05, values are means±S.Ds. TUNEL: transferasemediated dUTP nick end labelihg, I/R: ischemia-reperfusion, Cur: curcumin.

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