Journal
CIRCULATION-HEART FAILURE
Volume 4, Issue 1, Pages 79-88Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCHEARTFAILURE.110.957969
Keywords
ginsenosides; phenylephrine; NHE-1; calcineurin; heart failure
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Funding
- Institute of Circulatory and Respiratory Health of the Canadian Institutes of Health Research
- Ontario Ginseng Innovation and Research Consortium (OGIRC) (Ontario Ministry of Research and Innovation [RE02-049]
- OGIRC
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Background-Ginseng is a medicinal plant used widely in Asia that has gained popularity in the West during the past decade. Increasing evidence suggests a therapeutic role for ginseng in the cardiovascular system. The pharmacological properties of ginseng are mainly attributed to ginsenosides, the principal bioactive constituents in ginseng. The present study was carried out to determine whether ginseng exerts a direct antihypertrophic effect in cultured cardiomyocytes and whether it modifies the heart failure process in vivo. Moreover, we determined the potential underlying mechanisms for these actions. Methods and Results-Experiments were performed on cultured neonatal rat ventricular myocytes as well as adult rats subjected to coronary artery ligation (CAL). Treatment of cardiomyocytes with the alpha(1) adrenoceptor agonist phenylephrine (PE) for 24 hours produced a marked hypertrophic effect as evidenced by significantly increased cell surface area and ANP gene expression. These effects were attenuated by ginseng in a concentration-dependent manner with a complete inhibition of hypertrophy at a concentration of 10 mu g/mL. Phenylephrine-induced hypertrophy was associated with increased gene and protein expression of the Na+-H+ exchanger 1 (NHE-1), increased NHE-1 activity, increased intracellular concentrations of Na+ and Ca2(+), enhanced calcineurin activity, increased translocation of NFAT3 into nuclei, and GATA-4 activation, all of which were significantly inhibited by ginseng. Upregulation of these systems was also evident in rats subjected to 4 weeks of CAL. However, animals treated with ginseng demonstrated markedly reduced hemodynamic and hypertrophic responses, which were accompanied by attenuation of upregulation of NHE-1 and calcineurin activity. Conclusions-Taken together, our results demonstrate a robust antihypertrophic and antiremodeling effect of ginseng, which is mediated by inhibition of NHE-1-dependent calcineurin activation. (Circ Heart Fail. 2011;4:79-88.)
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