β-Caryophyllene inhibits Fas- receptor and caspase-mediated apoptosis signaling pathway and endothelial dysfunction in experimental myocardial infarction

J Biochem Mol Toxicol. 2021 Dec;35(12):e22907. doi: 10.1002/jbt.22907. Epub 2021 Nov 23.

Abstract

We planned to appraise the effects of β-caryophyllene on Fas- receptor and caspase-mediated apoptosis signaling pathway and endothelial dysfunction in rats infarcted with isoproterenol. Rats were induced myocardial infarction by using isoproterenol (100 mg/kg body weight [b.w]). Serum creatine kinase-MB, serum cardiac troponin-T, heart weight, heart rate, and heart lipid peroxidation were greatly (p < 0.05) augmented, while heart enzymatic antioxidants and plasma nonenzymatic antioxidants were greatly (p < 0.05) lessened in isoproterenol-treated rats. Reverse transcription-polymerase chain reaction study revealed augmented expressions of Fas-receptor and caspases 8, 9, and 3 genes in myocardial infarcted rats. Furthermore, iNOS protein expression was amplified and eNOS protein was lessened in the myocardial infarcted heart. Three weeks pre- and cotreatment with β-caryophyllene (20 mg/kg b.w) greatly (p < 0.05) protected isoproterenol-treated rats against these altered structural, biochemical, molecular, and immunohistochemical parameters, by its anti-cardiac hypertrophic, anti-tachycardial, antioxidant, anti-apoptotic, and anti-endothelial dysfunction effects. In conclusion, these findings projected the use of β-caryophyllene for the therapy of human myocardial infarction after clinical trials.

Keywords: antioxidants; isoproterenol; lipid peroxidation; myocardial infarction; β-caryophyllene.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Biomarkers / blood
  • Caspase Inhibitors / pharmacology*
  • Caspases / metabolism*
  • Creatine Kinase, MB Form / blood
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Heart Rate / drug effects
  • Male
  • Myocardial Infarction / metabolism*
  • Myocardium / enzymology
  • Myocardium / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Organ Size / drug effects
  • Oxidative Stress / drug effects
  • Polycyclic Sesquiterpenes / administration & dosage
  • Polycyclic Sesquiterpenes / pharmacology*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • fas Receptor / antagonists & inhibitors*
  • fas Receptor / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • Caspase Inhibitors
  • Polycyclic Sesquiterpenes
  • fas Receptor
  • caryophyllene
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Creatine Kinase, MB Form
  • Caspases