Cordycepin, 3-Deoxyadenosine, Prevents Rat Hearts from Ischemia/Reperfusion Injury Via Activation of Akt/GSK-3β/p70S6K Signaling Pathway and HO-1 Expression
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- 作者：Eun-Seok Park (1)
Do-Hyun Kang (1)
Min-Kyu Yang (1)
Jun Chul Kang (1)
Yong Chang Jang (1)
Jong Seok Park (2)
Si-Kwan Kim (1)
Hwa-Sup Shin (1) - 关键词：Cordycepin ; Ischemia/reperfusion ; Survival pathway ; Antioxidant
- 刊名：Cardiovascular Toxicology
- 出版年：2014
- 出版时间：March 2014
- 年：2014
- 卷：14
- 期：1
- 页码：1-9
- 全文大小：527 KB
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Do-Hyun Kang (1)
Min-Kyu Yang (1)
Jun Chul Kang (1)
Yong Chang Jang (1)
Jong Seok Park (2)
Si-Kwan Kim (1)
Hwa-Sup Shin (1)
1. Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, 322 Danwol-Dong, Chungju, Chungbuk, 380-701, Republic of Korea
2. Department of Biomedical Laboratory Science, Taegu Health College, Taegu, 702-722, Republic of Korea - ISSN：1559-0259
文摘
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.