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Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK.
J Cardiovasc Pharmacol Ther. 2012 Dec; 17(4):387-94.JC

Abstract

BACKGROUND

Curcumin, the active ingredient of turmeric (Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases.

METHODS

Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3β]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3β, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion.

RESULTS

Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3β, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3β induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3β compared with the control.

CONCLUSIONS

Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3β, and attenuation of p38 and JNK.

Authors+Show Affiliations

Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22396328

Citation

Jeong, Cheol-Won, et al. "Curcumin Protects Against Regional Myocardial Ischemia/reperfusion Injury Through Activation of RISK/GSK-3β and Inhibition of P38 MAPK and JNK." Journal of Cardiovascular Pharmacology and Therapeutics, vol. 17, no. 4, 2012, pp. 387-94.
Jeong CW, Yoo KY, Lee SH, et al. Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. J Cardiovasc Pharmacol Ther. 2012;17(4):387-94.
Jeong, C. W., Yoo, K. Y., Lee, S. H., Jeong, H. J., Lee, C. S., & Kim, S. J. (2012). Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. Journal of Cardiovascular Pharmacology and Therapeutics, 17(4), 387-94. https://doi.org/10.1177/1074248412438102
Jeong CW, et al. Curcumin Protects Against Regional Myocardial Ischemia/reperfusion Injury Through Activation of RISK/GSK-3β and Inhibition of P38 MAPK and JNK. J Cardiovasc Pharmacol Ther. 2012;17(4):387-94. PubMed PMID: 22396328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. AU - Jeong,Cheol-Won, AU - Yoo,Kyung Yeon, AU - Lee,Seong Heon, AU - Jeong,Hye Jin, AU - Lee,Cha Sup, AU - Kim,Seok Jai, Y1 - 2012/03/06/ PY - 2012/3/8/entrez PY - 2012/3/8/pubmed PY - 2013/4/20/medline SP - 387 EP - 94 JF - Journal of cardiovascular pharmacology and therapeutics JO - J Cardiovasc Pharmacol Ther VL - 17 IS - 4 N2 - BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases. METHODS: Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3β]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3β, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion. RESULTS: Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3β, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3β induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3β compared with the control. CONCLUSIONS: Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3β, and attenuation of p38 and JNK. SN - 1940-4034 UR - https://www.unboundmedicine.com/medline/citation/22396328/Curcumin_protects_against_regional_myocardial_ischemia/reperfusion_injury_through_activation_of_RISK/GSK_3β_and_inhibition_of_p38_MAPK_and_JNK_ L2 - https://journals.sagepub.com/doi/10.1177/1074248412438102?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -