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

Journal of Pharmacological Sciences

Masafumi Funamoto⁵  Yoichi Sunagawa⁵  Hideaki Kakeya¹  Ryuzo Sakata⁶  Shogo Sono⁵  Sae Hirano⁵  Hiromichi Wada⁴  Tatsuya Morimoto⁵  Yusuke Miyazaki⁵  Morio Ueno²  Yuya Hojo⁵  Koji Hasegawa⁴  Akira Marui⁶  Eriko Morimoto³  Hidetoshi Suzuki⁵  Yasufumi Katanasaka⁵ 

[1] Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan;Department of Ophthalmology, Kyoto Prefectural University of Medicine, Japan;Shizuoka General Hospital, Japan;Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Japan;Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan;Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Japan

关键词: curcumin;    heart failure;    hypertrophy;    dose-dependency;    p300;   

DOI  :  10.1254/jphs.14151FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(44)Cited-By(1)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.

【 授权许可】

Unknown