Curcumin reduces the cardiac ischemia-reperfusion injury: involvement of the toll-like receptor 2 in cardiomyocytes

J Nutr Biochem. 2012 Nov;23(11):1514-23. doi: 10.1016/j.jnutbio.2011.10.004. Epub 2012 Mar 7.

Abstract

Curcumin, a polyphenolic compound derived from turmeric, has protective effects on myocardial injury through attenuation of oxidative stress and inflammation. Toll-like receptor 2 (TLR2), a key mediator of the innate immune system, is involved in myocardial infarction and examined if controlled by curcumin. Rat cardiomyocytes (CMs) were stimulated with tumor necrosis factor (TNF)-α, peptidoglycan (PGN) or hypoxia/reoxygenation (H/R) with or without curcumin pretreatment. Sprague-Dawley rats were fed curcumin (300 mg/kg/day) 1 week before cardiac ischemia/reperfusion (I/R) injury. The expression level of TLR2 and cardiac function were assessed. Both mRNA and protein of TLR2 were up-regulated in infarcted myocardium, while TLR4 remained unchanged. In CMs, TLR2 and monocyte chemoattractant protein (MCP)-1 mRNAs were increased by TNF-α, PGN or H/R, whereas they were blunted by curcumin. Immunofluorescence staining of CMs also showed that TLR2 and MCP-1 were increased after H/R, whereas curcumin-pretreated CMs were not. In animal study, 2 weeks after I/R, TLR2 was increased in the infarct zone, whereas it stayed unchanged in the Cur+I/R group. Macrophage infiltration (CD68), high-mobility group box 1 and fibrosis were increased in the I/R group, whereas they were decreased in the Cur+I/R group. Connexin 43 was reduced in the I/R group, while it recovered significantly in the Cur+I/R group. Cardiac contractility in the Cur+I/R group was also improved compared with that in the I/R group (max dp/dt in Cur+I/R group: 9660±612 vs. I/R group: 8119±366, P<.05). These results suggest that selective inhibition of TLR2 by curcumin could be preventive and therapeutic for myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Curcumin / pharmacology*
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism
  • Male
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Peptidoglycan / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Cardiotonic Agents
  • Ccl2 protein, rat
  • Chemokine CCL2
  • HMGB1 Protein
  • Hbp1 protein, rat
  • Peptidoglycan
  • Tlr2 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Curcumin