Optimal Dose-Setting Study of Curcumin for Improvement of Left Ventricular Systolic Function After Myocardial Infarction in Rats

• Main Authors: Yoichi Sunagawa, Shogo Sono, Yasufumi Katanasaka, Masafumi Funamoto, Sae Hirano, Yusuke Miyazaki, Yuya Hojo, Hidetoshi Suzuki, Eriko Morimoto, Akira Marui, Ryuzo Sakata, Morio Ueno, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
• Format: Article
• Language: English
• Published: Elsevier 2014-04-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S134786131930091X

Abstract.: A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg−1∙day−1), a medium dose of curcumin (5 mg∙kg−1∙day−1), or a high dose of curcumin (50 mg∙kg−1∙day−1). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg−1∙day−1 and disappear at 0.5 mg∙kg−1∙day−1. To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required. Keywords:: curcumin, heart failure, hypertrophy, dose-dependency, p300