The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats

J Clin Invest. 2008 Mar;118(3):868-78. doi: 10.1172/JCI33160.


Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event in this process is nuclear acetylation by histone deacetylases and p300, an intrinsic histone acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for the yellow color of the spice turmeric, possesses HAT inhibitory activity with specificity for the p300/CREB-binding protein. We found that curcumin inhibited the hypertrophy-induced acetylation and DNA-binding abilities of GATA4, a hypertrophy-responsive transcription factor, in rat cardiomyocytes. Curcumin also disrupted the p300/GATA4 complex and repressed agonist- and p300-induced hypertrophic responses in these cells. Both the acetylated form of GATA4 and the relative levels of the p300/GATA4 complex markedly increased in rat hypertensive hearts in vivo. The effects of curcumin were examined in vivo in 2 different heart failure models: hypertensive heart disease in salt-sensitive Dahl rats and surgically induced myocardial infarction in rats. In both models, curcumin prevented deterioration of systolic function and heart failure-induced increases in both myocardial wall thickness and diameter. From these results, we conclude that inhibition of p300 HAT activity by the nontoxic dietary compound curcumin may provide a novel therapeutic strategy for heart failure in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cardiomegaly / prevention & control
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • DNA / metabolism
  • Enzyme Inhibitors / pharmacology*
  • GATA4 Transcription Factor / metabolism
  • Heart Failure / prevention & control*
  • Hypertension / complications
  • Male
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / physiopathology
  • Myocytes, Cardiac / drug effects
  • Rats
  • Systole / drug effects
  • Ventricular Function, Left / drug effects
  • p300-CBP Transcription Factors / antagonists & inhibitors*


  • Enzyme Inhibitors
  • GATA4 Transcription Factor
  • DNA
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Curcumin