Curcumin protects hearts from FFA-induced injury by activating Nrf2 and inactivating NF-κB both in vitro and in vivo

J Mol Cell Cardiol. 2015 Feb:79:1-12. doi: 10.1016/j.yjmcc.2014.10.002. Epub 2014 Oct 16.

Abstract

Obesity and increased free fatty acid (FFA) level are tightly linked, leading to the development of cardiovascular disorders. Curcumin is a natural product from Curcuma longa with multiple bioactivities and is known to have cardioprotective effects in several cellular and animal models. The current study was designed to evaluate the cardioprotective effects of curcumin and demonstrate the underlying mechanism in FFA-induced cardiac injury. Using cell culture studies and high fat in vivo model, we explored the mechanistic basis of anti-inflammatory and antioxidant activities of curcumin. We observed that palmitate (PA) treatment in cardiac derived H9C2 cells induced a marked increase in reactive oxygen species, inflammation, apoptosis and hypertrophy. All of these changes were effectively suppressed by curcumin treatment. In addition, oral administration of curcumin at 50mg/kg completely suppressed high fat diet-induced oxidative stress, inflammation, apoptosis, fibrosis, hypertrophy and tissue remodeling in mice. The beneficial actions of curcumin are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Thus, both in vitro and in vivo studies showed a promising role of curcumin as a cardioprotective agent against palmitate and high fat diet mediated cardiac dysfunction. We indicated the regulatory roles of Nrf2 and NF-κB in obesity-induced heart injury, and suggested that they may be important therapeutic targets in the treatment of obesity-related disorders.

Keywords: Cardioprotection; Curcumin; Free fatty acids; Inflammation; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Cardiomegaly / complications
  • Cardiomegaly / drug therapy
  • Cardiomegaly / pathology
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cell Line
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Diet, High-Fat
  • Fatty Acids, Nonesterified / adverse effects*
  • Fibrosis
  • Male
  • Mice, Inbred C57BL
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects
  • Palmitates / adverse effects
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cardiotonic Agents
  • Fatty Acids, Nonesterified
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Palmitates
  • Reactive Oxygen Species
  • Curcumin