Novel oral curcumin drug-delivery system improves the deterioration of systolic function after rat myocardial infarction

Novel oral curcumin drug-delivery system improves the deterioration of systolic function after rat myocardial infarction

Yoichi Sunagawa1,5, Hiroyuki Fukuda2, Hiromichi Wada1, Tomohide Takaya1,4, Teruhisa Kawamura1, Akira Simatsu6, Takeshi Kimura4, Masatoshi Fujita5, Koji Hasegawa1, Tatsuya Morimoto3.

  1. Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Proteomics Research Center, Theravalues Corporation, Osaka, Japan.
  3. Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  4. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  5. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  6. Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.

第13回日本心不全学会学術集会 (横浜), 2009/10/16-18.

Abstract

Purpose: Recently, we found that curcumin (50 mg/kg/day), a natural compound that inhibits p300 histone acetyltransferase activity, prevents the deterioration of the systolic function in two different rat heart failure models. To achieve efficient oral pharmacological therapy for heart failure, we have established a novel curcumin drug-delivery system (DDS) that increases plasma curcumin levels.

Methods: We generated a curcumin-containing drug using an emulsifying agent which contains gum ghatti. One week after coronary ligation, 36 rats were randomly assigned to treatment with gum ghatti (vehicle control), native curcumin (0.5 mg/kg/day), or curcumin in gum ghatti (DDS curcumin, 0.5 mg/kg/day) for 6 weeks.

Results: There were no differences among the 3 groups in all LV geometric and functional data examined before the treatment. After treatment, LVFS was significantly (p < 0.05) greater in DDS curcumin (26.0±0.9%) than in vehicle control (13.8±0.7%) or native curcumin (14.1±0.9%). The LV wall thickness was significantly thinner in DDS curcumin than in vehicle control or native curcumin. The plasma concentration of curcumin was 60-fold higher in rats orally administered DDS curcumin than those given native curcumin.

Conclusions: Orally administering a low dose of DDS curcumin, but not that of native curcumin, improves post-MI LV systolic dysfunction in rats. Thus, this novel DDS of curcumin may be useful in long-term pharmacological therapy for heart failure in the clinical setting.