Email updates

Keep up to date with the latest news and content from Cardiovascular Diabetology and BioMed Central.

Open Access Open Badges Original investigation

Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

Yi-Jin Ho1, An-Sheng Lee2, Wen-Pin Chen1, Wei-Lung Chang1, Ying-Kang Tsai1, Hsi-Lin Chiu3, Yueh-Hsiung Kuo45 and Ming-Jai Su1*

Author Affiliations

1 Department of Pharmacology, College of Medicine, National Taiwan University, 11F, No. 1, Sec. 1, Jen-Ai Road, Taipei 10051, Taiwan

2 Department of Medicine, Mackay Medical College, New Taipei 252, Taiwan

3 Department of Chemistry, National Taiwan University, Taipei 100, Taiwan

4 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

5 Department of Biotechnology, Asia University, Taichung 413, Taiwan

For all author emails, please log on.

Cardiovascular Diabetology 2014, 13:98  doi:10.1186/1475-2840-13-98

Published: 12 June 2014



Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats.


Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-L-arginine methyl ester [L-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats.


Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (L-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals.


CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals.

Diabetes; Ischemia/reperfusion injury; Caffeic acid phenethyl amide