Abstract 11035: Nobiletin, a Citrus Flavonoid, Prevents The development of Heart Failure After Myocardial Infarction in Rats
Introduction: Maladaptive hypertrophy is being recognized as a critical event during the development of heart failure. We screened natural compounds purified from a citrus fruits library and found that a natural compound, nobiletin, could inhibit cardiomyocyte hypertrophy in culture. Nobiletin has various useful effects such as anti-cancer, anti-inflammation, and anti-oxidant and may be applicable to pharmacological therapy for heart failure. Hypothesis: We thought that nobiletin might prevent the deterioration of cardiac function after myocardial infarction (MI) in rats.
Methods and Results: 1) In primary cardiomyocytes prepared from neonatal rats, nobiletin, at the concentration of 150 nM, repressed phenylephrine-induced hypertrophic responses such as myofibrillar organization, increased cell size and transcriptional activation. 2) Adult rats were subjected to sham operation or MI. One week later, the rats with a moderate size of MI (LVFS<40%) were randomly assigned to a control vehicle (n=5) or a nobiletin (20 mg/kg/day) (n=5) group. Oral daily treatments with these agents were continued for 6 weeks. There were no differences between the 2 groups with respect to any LV geometric and functional parameters examined by echocardiography at baseline. After treatment, LVFS was significantly (p<0.001) higher in the nobiletin (26%) than the control (17%) group. The LV wall thickness in the remote non-infarct area was significantly (p<0.001) thinner in the nobiletin (1.3mm) than the control (2.3 mm) group. Moreover, histological analysis demonstrated that myocardial cell diameter and perivascular fibrosis were significantly (p<0.05) smaller in the nobiletin than the control group. The mRNA expressions of ANF and ET-1 were decreased in the nobiletin group compared with in the control group.
Conclusions: Nobiletin, contained in natural fruits, represses hypertrophic responses in cardiomyocytes and prevents systolic functional deterioration and LV pathological growth after MI in vivo. Thus, this non-toxic dietary compound is expected as a novel useful agent for heart failure in humans.
- © 2012 by American Heart Association, Inc.