Phloretin Protects Against Cardiac Damage and Remodeling via Restoring SIRT1 and Anti-Inflammatory Effects in the Streptozotocin-Induced Diabetic Mouse Model

Aging (Albany NY). 2019 May 10;11(9):2822-2835. doi: 10.18632/aging.101954.

Abstract

Diabetic cardiomyopathy increases the risk of heart failure independent of coronary artery disease and hypertension. Phloretin (PHL) shows anti-inflammatory effects in macrophages. In this study, we explored the protective effects of PHL on high glucose (HG)-induced injury in diabetic cardiomyopathy in vivo and in vitro. Using streptozotocin-induced diabetic mouse model and incubating cardiac cells line under a HG environment, PHL were evaluated of the activities of anti-inflammation and anti-fibrosis. In the study, PHL treatment ameliorated cardiomyocyte inflammation injury, and reduced fibrosis in vivo and in vitro. PHL also improved cardiac biochemical criterions after 8 weeks of induction of diabetes in C57BL/6 mice. Molecular docking results indicated that silent information regulator 2 homolog 1 (SIRT1) bound to PHL directly and that SIRT1 expression was upregulated in the PHL-treated group in HG-induced H9C2 cells. Protective effect of PHL was been eliminated in silence SIRT1 H9C2 cells. Taken together, these results suggested that PHL suppressed HG-induced cardiomyocyte injury via restoring SIRT1 expression.

Keywords: SIRT1; anti-inflammation; diabetic cardiomyopathy; phloretin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Cardiomyopathies / prevention & control*
  • Fibrosis / prevention & control
  • Gene Expression Regulation / drug effects
  • Inflammation / prevention & control*
  • Mice
  • Myocytes, Cardiac / drug effects
  • Phloretin / pharmacology*
  • Rats
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*

Substances

  • Sirt1 protein, mouse
  • Sirt1 protein, rat
  • Sirtuin 1
  • Phloretin