The effects of ginsenoside Rb1 on fatty acid β-oxidation, mediated by AMPK, in the failing heart.

Objectives: This study intended to investigate the effects of Ginsenoside-Rbl (Gs-Rbl) on fatty acid β-oxidation (FAO) in rat failing heart and to identify potential mechanisms of Gs-Rbl improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK).

Materials and Methods: Rats with chronic HF, induced by adriamycin ( Adr ), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-β-D-arabinofuranoside ( Ara A , specific AMPK inhibitor), and 5'-aminoimidazole-4-carboxamide riboside ( Aicar , specific AMPK activator) were administered to rats with HF, singly and/or combinedly. Myocardial high-energy phosphate (such as phosphocreatine, ADP, and ATP), free L-Carnitine, malonyl-CoA, and the activity of FAO-related enzymes in left ventricle from different groups were measured by using the corresponding molecular biological techniques.

Results: Gs-Rb1 improved HF significantly, accompanied by a significant increase in phosphocreatine (PCr), ADP, ATP, PCr/ATP ratio, free carnitine, malonyl-CoA, mRNA, activity of carnitine palmitoyltransferase (Cpt), medium-chain Acyl-CoA Dehydrogenase (MCAD) and long-chain acyl-CoA Synthetase (ACSL) and a significant decrease of the ADP/ATP ratio in the left ventricular myocardium. However, all those effects were almost abolished by Ara A and were not further improved by Aicar .

Conclusion: Taken together, it suggests that Gs-Rb1 may modulate cardiac metabolic remodeling by improving myocardial fatty acid β-oxidation in failing heart. In addition, the effects of Gs-Rb1 may be mediated via activating AMPK.