Cordycepin, 3'-deoxyadenosine, prevents rat hearts from ischemia/reperfusion injury via activation of Akt/GSK-3β/p70S6K signaling pathway and HO-1 expression

Cardiovasc Toxicol. 2014 Mar;14(1):1-9. doi: 10.1007/s12012-013-9232-0.


Cordycepin (3'-deoxyadenosine) isolated from Cordyceps militaris, a species of the fungal genus Cordyceps, has been shown to exhibit many pharmacological functions, such as anticancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the preventive role of cordycepin in ischemic/reperfusion (I/R) injury of isolated rat hearts and anesthetized rats. After Sprague-Dawley rats received cordycepin (3, 10, and 30 mg/kg) or control (0.5 % carboxyl methylcellulose) orally once a day for a week, hearts were isolated and mounted on Langendorff heart perfusion system. Isolated hearts were perfused with Krebs-Henseleit buffer for 15-min pre-ischemic stabilization period and subjected to 30-min global ischemia and 30-min reperfusion. Cordycepin administration (10 mg/kg, p.o.) significantly increased left ventricular developed pressure during the reperfusion period compared to that in the control group, but without any effect on coronary flow. Cordycepin (10 mg/kg, p.o.) significantly increased the phosphorylation of Akt/GSK-3β/p70S6K pathways, which are known to modulate multiple survival pathways. In addition, cordycepin decreased Bax and cleaved caspase-3 expression while increasing Bcl-2 expression, Bcl-2/Bax ratio, and heme oxygenase (HO-1) expression in isolated rat hearts. In anesthetized rats subjected to 30 min occlusion of left anterior descending coronary artery/2.5-h reperfusion, cordycepin (1, 3, and 10 mg/kg, i.v.) administered 15 min before the onset of ischemia dose-dependently decreased the infarct size in left ventricle. In conclusion, cordycepin could be an attractive therapeutic candidate with oral activity against I/R-associated heart diseases such as myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology*
  • Cordyceps / metabolism
  • Cytoprotection
  • Deoxyadenosines / isolation & purification
  • Deoxyadenosines / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Male
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / enzymology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / enzymology*
  • Myocardium / pathology
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / drug effects*
  • Time Factors
  • Ventricular Function, Left / drug effects
  • Ventricular Pressure / drug effects


  • Apoptosis Regulatory Proteins
  • Cardiotonic Agents
  • Deoxyadenosines
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Glycogen Synthase Kinase 3
  • cordycepin