Aspernolide F, as a new cardioprotective butyrolactone against doxorubicin-induced cardiotoxicity

Int Immunopharmacol. 2019 Jul;72:429-436. doi: 10.1016/j.intimp.2019.04.045.


Endophytic fungi have known as a promising source of secondary metabolites. γ-Butyrolactones are a class of metabolites reported from Aspergillus genus, which attracted much attention for their bioactivities. This study aimed to assess the potential cardioprotective effects of aspernolide F (AF) separated from the endophytic fungus A. terreus against doxorubicin (DOX)-induced cardiotoxic effects in rats. Animals were treated with two different doses of AF for 10 days prior to DOX injection. Electrocardiographic (ECG), biochemical, histopathological and immunohistochemical analyses were performed. Results have shown that AF effectively protected against DOX-induced cardiac damage as AF counteracted DOX-induced ECG abnormalities and attenuated serum markers of cardiotoxicity (creatine kinase-MB, lactate dehydrogenase, troponin I, and troponin T). Histopathological examination of cardiac tissue revealed a remarkable improvement in DOX-induced lesions. In addition, AF ameliorated DOX-induced oxidative damage and increased the levels of antioxidants in cardiac tissues. AF treatment inhibited the activation of nuclear factor-κB (NF-κB) and decreased the immuno-expression of NF-κB in cardiac tissue. Furthermore, AF caused a marked lowering in the level of inflammatory cytokines (nitric oxide, tumor necrosis factor-α, and interleukin-6) in the cardiac tissue. Collectively, this study demonstrates the cardioprotective activity of AF against DOX-induced cardiac damage which may be due to its antioxidant and anti-inflammatory activities.

Keywords: Aspergillus terreus; Aspernolide F; Cardiotoxicity; Doxorubicin; NF-κB; γ-Butyrolactones.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Aspergillus
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cardiotoxicity / drug therapy*
  • Cardiotoxicity / metabolism
  • Doxorubicin
  • Interleukin-6 / metabolism
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibiotics, Antineoplastic
  • Antioxidants
  • Cardiotonic Agents
  • Il6 protein, rat
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Doxorubicin