Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro

Drug Des Devel Ther. 2016 Mar 29;10:1267-77. doi: 10.2147/DDDT.S104925. eCollection 2016.

Abstract

Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI) are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs) with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1) in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart.

Keywords: SIRT1; angiotensin II; cardiac fibroblasts; curcumin; fibrosis; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Cells, Cultured
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Enzyme Activation / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis / drug therapy
  • Fibrosis / etiology*
  • Fibrosis / pathology
  • Fibrosis / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / complications*
  • Myocardial Infarction / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Rats
  • Rats, Wistar
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Structure-Activity Relationship

Substances

  • Angiotensin II
  • Sirt1 protein, mouse
  • Sirt1 protein, rat
  • Sirtuin 1
  • Curcumin