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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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Abstract

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.

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Abbreviations

CF:

Coronary flow

CMC:

Carboxyl methylcellulose

ERK:

Extracellular signal-regulated kinase

LVDL:

Left ventricular developed pressure

LVEDP:

Left ventricular end-diastolic pressure

XTT:

2,3-Bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide

PVDF:

Polyvinylidene fluoride

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

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Acknowledgments

This study was supported by the Konkuk University.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, 322 Danwol-Dong, Chungju, Chungbuk, 380-701, Republic of Korea

    Eun-Seok Park, Do-Hyun Kang, Min-Kyu Yang, Jun Chul Kang, Yong Chang Jang, Si-Kwan Kim & Hwa-Sup Shin

  2. Department of Biomedical Laboratory Science, Taegu Health College, Taegu, 702-722, Republic of Korea

    Jong Seok Park

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  1. Eun-Seok Park
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Correspondence to Hwa-Sup Shin.

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Eun-Seok Park and Do-Hyun Kang have contributed equally to this work.

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Park, ES., Kang, DH., Yang, MK. et al. 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 14, 1–9 (2014). https://doi.org/10.1007/s12012-013-9232-0

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