Suppression of isoproterenol-induced cardiotoxicity in rats by raspberry ketone via activation of peroxisome proliferator activated receptor-α

Eur J Pharmacol. 2019 Jan 5:842:157-166. doi: 10.1016/j.ejphar.2018.10.034. Epub 2018 Oct 26.


The peroxisome proliferator-activated receptor-α (PPAR-α) controls the lipid and glucose metabolism and also affects inflammation, cell proliferation and apoptosis during cardiovascular disease. Raspberry ketone (RK) is a red raspberry (Rubusidaeus, Family-Rosaceae) plant constituent, which activates PPAR-α. This study was conducted to assess the cardioprotective action of RK against isoproterenol (ISO)-induced cardiotoxicity. Wistar rats were randomly divided into six groups (six rats/group). Rats were orally administered with RK (50, 100 and 200 mg/kg, respectively) and fenofibrate (standard, 80 mg/kg) for 28 days and ISO was administered (85 mg/kg, subcutaneously) on 27th and 28th day. Administration of ISO in rats significantly altered hemodynamic and electrocardiogram patterns, total antioxidant capacity, PPAR-α, and apolipoprotein C-III levels. These myocardial aberrations were further confirmed during infarct size, heart weight to body weight ratio and immunohistochemical assessments (caspase-3 and nuclear factor-κB). RK pretreatment (100 and 200 mg/kg) significantly protected rats against oxidative stress, inflammation, and dyslipidemia caused by ISO as demonstrated by change in hemodynamic, biochemical and histological parameters. The results so obtained were quite comparable with fenofibrate. Moreover, RK was found to have binding affinity with PPAR-α, as confirmed by docking analysis. PPAR-α expression and concentration was also found increased in presence of RK which gave impression that RK probably showed cardioprotection via PPAR-α activation, however direct binding study of RK with PPAR-α is needed to confirm this assumption.

Keywords: Apolipoprotein C-III; Fenofibrate; Isoproterenol; Myocardial infarction; PPAR-α; Raspberry ketone.

MeSH terms

  • Animals
  • Apolipoprotein C-II / metabolism
  • Butanones / metabolism
  • Butanones / pharmacology*
  • Butanones / therapeutic use
  • Cardiotonic Agents / metabolism
  • Cardiotonic Agents / pharmacology*
  • Cardiotonic Agents / therapeutic use
  • Caspase 3 / genetics
  • Electrocardiography
  • Gene Expression Regulation, Enzymologic / drug effects
  • Heart / drug effects*
  • Heart / physiology
  • Hemodynamics / drug effects
  • Isoproterenol / antagonists & inhibitors
  • Isoproterenol / toxicity*
  • Male
  • Molecular Docking Simulation
  • Myocardial Infarction / drug therapy
  • NF-kappa B / genetics
  • PPAR alpha / chemistry
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Protein Conformation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar


  • Apolipoprotein C-II
  • Butanones
  • Cardiotonic Agents
  • NF-kappa B
  • PPAR alpha
  • RNA, Messenger
  • raspberry ketone
  • Caspase 3
  • Isoproterenol