title: Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK.
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.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Cheol-Won
authors.initials: CW
authors.lastname: Jeong
authors.forename: Kyung Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Seong Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Cha Sup
authors.initials: CS
authors.lastname: Lee
authors.forename: Seok Jai
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D003474:Curcumin / Q000737:chemistry / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006352:Heart Ventricles / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007211:Indoles / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008301:Maleimides / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D000081082:Phosphoinositide-3 Kinase Inhibitors; C417521:SB 216763; D058539:Phosphatidylinositol 3-Kinase; C494920:Akt1 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin