A novel drug-delivery system of oral curcumin markedly improves efficiency of heart failure treatment after myocardial infarction in rats

A novel drug-delivery system of oral curcumin markedly improves efficiency of heart failure treatment after myocardial infarction in rats

Yoichi Sunagawa1, Hiroyuki Fukuda2, Hiromichi Wada3, Tomohide Takaya3, Akira Marui5, Kazuhide Uemura4, Akira Shimatsu3, Masatoshi Fujita1, Koji Hasegawa3, Tatsuya Morimoto4.

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

第74回日本循環器学会学術集会 (京都), 2010/03/05 (ポスター).

Abstract

Purpose: We found that curcumin, a natural compound that inhibits p300 histone acetyltransferase activity, prevents the deterioration of systolic function in two different rat models of heart failure. To achieve more efficient oral pharmacological therapy for heart failure by curcumin, we have developed a new drug-delivery system (DDS).

Methods: We generated a curcumin-containing drug with use of an emulsifying agent which contains gum ghatti. Rats were subjected to sham operation or MI. One week later, the rats with moderate size of MI were randomly assigned to 3 groups: I: vehicle control (n = 12), II: native curcumin (0.5 mg/kg/day, n = 12), III: curcumin in gum ghatti (DDS-curcumin, 0.5 mg/kg/day, n = 12). Oral treatments by these agents were repeated every day and contributed for 6 weeks.

Results: There were no differences among 3 groups with respect to all LV geometric and functional data examined before treatment. After treatment, LV fractional shortening was significantly (p < 0.05) higher in the group III (26.0%) than the group I (13.8%) or II (14%). LV wall thickness was significantly (p < 0.05) thinner in the group III (1.3 mm) than the group I (2.6 mm) or II (2.3 mm). We found that plasma concentration of curcumin was 60-fold higher in the group III compared with ghe group II.

Conclusion: Our new DDS-curcumin markedly improves the efficacy of heart failure treatment and will be applicable to the human clinical setting.