Ginseng Inhibits Cardiomyocyte Hypertrophy and Heart Failure via NHE-1 Inhibition and Attenuation of Calcineurin Activation

Abstract

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 ␣ 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 g/mL. Phenylephrine-induced hypertrophy was associated with increased gene and protein expression of the Na

Ginseng Reverses Established Cardiomyocyte Hypertrophy and Postmyocardial Infarction-Induced Hypertrophy and Heart Failure

“…However, work from our laboratory and that of others has clearly demonstrated marked left ventricular systolic and diastolic dysfunction as early as 1 week after CAL, which is well established at the 4-week period. 9,[18][19][20] We have confirmed this in the present study in rats (N=5) subjected to catheter-based left ventricular function assessment 4 weeks after CAL. These animals demonstrated a 3-fold increase in left ventricular end-diastolic pressure and a 21% reduction in left ventricular end-systolic pressure compared with rats subjected to sham procedure, accompanied by a 43% increase in the left ventricular weight/body weight values (data not shown).…”

“…Among these traditional Chinese medicines, North American ginseng (Panax quinquefolius) as well as other ginseng varieties have been garnering increasing interest in western societies for their salutary effects on the cardiovascular system. 8 Recently, we have demonstrated a robust ability of North American ginseng to prevent cardiomyocyte hypertrophy and heart failure through a mechanism likely involving prevention of calcineurin activation, 9 the latter representing a key factor for myocardial hypertrophy and remodeling. 10,11 In view of a recent study indicating calcineurin-dependent cardiac hypertrophy as a reversible process 12 and the potential importance of calcineurin as a target for the antihypertrophic effect of ginseng, we determined whether the latter can reverse already-established hypertrophy and heart failure using both in vitro and in vivo approaches.…”

“…9 A 2.0F P-V Mikro-Tip catheter (Millar Instruments) was retrogradely inserted into the left ventricle through the right carotid artery. Hemodynamic data were recorded and analyzed using Notocord-Hem 4.2 software (Notocord) digitized with a sampling rate of 1000 Hz.…”

Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress

“…Both genes are also expressed in the adult heart (Cameron et al, 1996;Houweling et al, 2005) but Nppa is downregulated in the ventricles around birth to become restricted to the atria and the ventricular conduction system (Moorman and Christoffels, 2003). Both genes are strongly induced in the ventricles by stress and heart failure, and have become reliable clinical and experimental biomarkers for the severity of hypertrophy and heart failure (Guo et al, 2011;Sergeeva et al, 2014;Troughton et al, 2014). Moreover, Nppa is an important marker of early developmental malformations leading to congenital heart defects (Bruneau, 2011).…”

Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca2+Entry and Ca2+Release in Beating Rabbit Atria

“…2 In addition, traditional Oriental medicine (TOM), recognized as one of the numerous complementary and alternative medicine modalities in the West, is very popular in the general population of Eastern world and several special herbal products with low side-effects have great potential for treating heart diseases. [3][4][5] Lycopus lucidus Turcz, a perennial herb known as ''Taekran'' in Korea and ''Zelan'' in China, has been widely used for centuries as a TOM. In China, ''Zelan'' recorded in the most famous original herbal classic ''Shennongbencao'' has the function of promoting blood circulation and removing blood stasis.…”