Isosteviol sodium attenuates high fat/high cholesterol-induced myocardial dysfunction by regulating the Sirt1/AMPK pathway

Biochem Biophys Res Commun. 2022 Sep 17:621:80-87. doi: 10.1016/j.bbrc.2022.06.044. Epub 2022 Jun 30.

Abstract

A fat-rich diet triggers obesity, and promotes cardiomyocyte injury. Till now, no prior investigations suggested a beneficial role of Isosteviol Sodium (STVNa) in cardiac activity in high fat diet (HFD)-exposed obese rats. However, there is evidence that STVNa accelerates healing of multiple tissue injuries. Herein, we explored the underlying mechanism behind the STVNa-based protection against HFD-induced myocardial dysfunction (MCD) in a rat model of myocardial injury. We employed dosages of 1, 10, and 20 mg/kg STVNa to treat MCD in rats fed with a HFD. Based on our results, STVNa repressed MCD (as indicated by ecocardiographic analysis), myocardium function, pathological structure, and myocardial enzymes. Mechanistically, the STVNa-mediated protection against HFD-induced MCD involved inhibition of inflammation and oxidative stress. Furthermore, using Western blot analysis, we revealed that the critical members of the Sirt1/AMPK network were markedly activated in the STVNa-treated group, relative to HFD-fed controls. Collectively, these evidences suggested that the STVNa offered strong protection against HFD-induced MCD. Moreover, this effect was mediated by the activation of the Sirt1/AMPK network, which, in turn, promoted lipid metabolism.

Keywords: AMPK; High-fat diet; Isosteviol sodium; Myocardium; Sirt1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Cardiomyopathies*
  • Cholesterol
  • Diet, High-Fat / adverse effects
  • Diterpenes, Kaurane
  • Obesity
  • Rats
  • Sirtuin 1* / metabolism
  • Sodium

Substances

  • Diterpenes, Kaurane
  • isosteviol
  • Cholesterol
  • Sodium
  • AMP-Activated Protein Kinases
  • Sirt1 protein, rat
  • Sirtuin 1