Rosmarinic acid ameliorated cardiac dysfunction and mitochondrial injury in diabetic cardiomyopathy mice via activation of the SIRT1/PGC-1α pathway

Biochem Biophys Res Commun. 2021 Mar 26:546:29-34. doi: 10.1016/j.bbrc.2021.01.086. Epub 2021 Feb 6.

Abstract

Mitochondrial injury plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Previous studies demonstrated that rosmarinic acid (RA) treatment prevented high glucose-induced mitochondrial injury in vitro. However, whether RA can ameliorate cardiac function by preventing mitochondrial injury in DCM is unknown. The SIRT1/PGC-1α pathway has emerged as an important regulator of metabolic control and other mitochondrial functions. The present study was undertaken to determine the effects of RA on mitochondrial and cardiac function in DCM as well as the involvement of the SIRT1/PGC-1α pathway. Our results revealed that RA improved cardiac systolic and diastolic function and prevented mitochondrial injury in DCM, as shown by the reduced blood glucose and lipid levels, increased mitochondrial membrane potential levels, improved adenosine triphosphate synthesis, and inhibited apoptosis (P < 0.05). Moreover, RA upregulated the expression of SIRT1 and PGC-1α in DCM mice and high glucose-treated H9c2 cardiomyocytes (P < 0.05). Further mechanistic studies in H9c2 cardiomyocytes revealed that suppression of SIRT1 by Sh-SIRT1 counteracted the effects of RA on high glucose-induced abnormal metabolism of glucose and lipids, oxidative stress and apoptosis (P < 0.05). Taken together, these data indicate that RA prevented mitochondrial injury and cardiac dysfunction in DCM mice, and the SIRT1/PGC-1α pathway mediated the protective effects of RA.

Keywords: Diabetic cardiomyopathy; Mitochondria; Rosmarinic acid; SIRT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cinnamates / antagonists & inhibitors
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use*
  • Depsides / antagonists & inhibitors
  • Depsides / pharmacology
  • Depsides / therapeutic use*
  • Diabetic Cardiomyopathies / drug therapy*
  • Diabetic Cardiomyopathies / physiopathology*
  • Glucose / pharmacology
  • Male
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / pathology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Oxidative Stress / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Rosmarinic Acid
  • Signal Transduction / drug effects
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / metabolism*

Substances

  • Cinnamates
  • Depsides
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Protective Agents
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Glucose