Nootkatone attenuates myocardial oxidative damage, inflammation, and apoptosis in isoproterenol-induced myocardial infarction in rats

M. F.Nagoor Meeran, Sheikh Azimullah, Ernest Adeghate, Shreesh Ojha

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


Background: Myocardial infarction (MI) is a lethal manifestation of cardiovascular diseases. Oxidative stress, inflammation, and subsequent cell death are known to play crucial roles in the pathogenesis of MI. Despite tremendous developments in interventional cardiology, there is need for novel drugs for the prevention and treatment of MI. For the development of novel drugs, usage of natural products has gained attention as a therapeutic approach for ischemic myocardial injury. Among many popular plant-derived compounds, Nootkatone (NKT), a natural bioactive sesquiterpene, abundantly found in grapefruit, has attracted attention for its plausible health benefits and pharmacological properties. Purpose: The present study investigated the cardioprotective effects of NKT in rats against MI induced by isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist that produces MI in a physiologically relevant manner. Methods: MI was induced in male Wistar albino rats by subcutaneous injection of ISO (85 mg/kg body weight) on 9th and 10th day. Rats were pre- and co-treated with NKT (10 mg/kg) through daily oral administration for eleven days. Results: ISO-induced MI was characterized by a significant decline in cardiac function, increased serum levels of cardiomyocyte injury markers, enhanced oxidative stress, and altered PI3K/Akt and NrF2/Keap1/HO-1 signaling pathways. ISO also elevated the levels of myocardial pro-inflammatory cytokines, promoted lysosomal dysfunction, altered TLR4-NFκB/MAPK signaling, and triggered intrinsic apoptotic pathway in heart tissues. However, NKT administration significantly restored or modulated majority of the altered biochemical and molecular parameters in ISO-treated rats. Furthermore, histopathological observations confirmed the myocardial restoring effect of NKT. Conclusion: The present study concludes the cardioprotective effects and underlying mechanisms of NKT against ISO-induced MI in rats, and suggests that NKT or plants containing NKT could be an alternative to cardioprotective agents in ischemic heart diseases.

Original languageEnglish
Article number153405
Publication statusPublished - Apr 2021


  • Apoptosis
  • Inflammation
  • Isoproterenol
  • Lysosomal dysfunction
  • Myocardial infarction
  • Nootkatone

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine


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