Cordycepin, 3'-Deoxyadenosine, Prevents Rat Hearts from Ischemia/Reperfusion Injury Via Activation of Akt/GSK-3[beta]/p70S6K Signaling Pathway and HO-1 Expression

• Published in: Cardiovascular toxicology Vol. 14; no. 1; p. 1
• Main Authors: Park, Eun-Seok, Kang, Do-Hyun, Yang, Min-Kyu, Kang, Jun Chul, Jang, Yong Chang, Park, Jong Seok, Kim, Si-Kwan
• Format: Journal Article
• Language: English
• Published: Totowa Springer 01.03.2014; Springer Nature B.V
• Subjects: Antioxidants; Heart; Heart attack; Ischemia; Laboratory animals; Oxidative stress; South Korea
• ISSN: 1530-7905; 1559-0259
• 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-3[beta]/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.