Total Ginsenosides Inhibit the Right Ventricular Hypertrophy Induced by Monocrotaline in Rats

Abstract

Ginseng, the root of Panax ginseng C. A. MEYER, is a wellknown and popular herbal medicine used in China for centuries and is now a world wide used natural medicine. Ginsenosides, the pharmacologically active components found in Ginseng, are also found in the leaf and stem of Panax ginseng C. A. MEYER, 1) and more than 30 different ginsenosides have been isolated from Ginseng. Ginsenosides exert various pharmacological effects on the central nervous, cardiovascular, endocrine, and immune systems.2-4) Notably, it is shown that Ginsenosides could reduce both Ca 2ϩ influx and catecholamine secretion in bovine adrenal chromaffin cells, 5,6) inhibit voltage-dependent Ca 2ϩ channels in sensory neurons as well as in chromaffin in cells, 7) and decrease the level of intracellular free calcium concentration ([Ca 2ϩ ] i ) in dog's myocardium suffered from ischemia-reperfusion injury 8) ; Ginsenosides could also stimulate endogenous product of nitric oxide (NO) in rat kidney 9) and in cardiovascular tissues, 10) evoke endothelium-dependent vascular relaxation in rat aorta. 11) Ca 2ϩ elevation has been known to be a critical signaling in the development of cardiac hypertrophy induced by various hypertrophic stimuli, 12) and NO, produced in virtually every cell type in the heart, shows potent antihypertrophic effects.13) Both effects of Ca 2ϩ -decrease and NO-release of ginsenosides indicate that ginsenosides may have a potential inhibitory effect on cardiac hypertrophy.The mechanism(s) at molecular level of pathological cardiac hypertrophy remains unclear. It has been reported that Ca 2ϩ elevation activates the calcineurin (CaN) pathway, and in turn enhances hypertrophy or apoptosis of cardiomyocytes.14) In addition, extracellular signal-regulated kinase-1/2 (ERK-1/2, the important members of mitogen-activated protein kinase (MAPK) family) likely occupies a central regulatory position in the signaling hierarchy of a cardiac myocyte given its unique ability to respond to virtually every characterized hypertrophic agonist and stress stimuli. 15) In the present study, we investigated whether total ginsenosides (TG) extracted from the leaf and stem of Panax ginseng C. A. MEYER have inhibitory effect on right ventricle hypertrophy (RVH) induced by injection of monocrotaline (MCT) which lead to pulmonary hypertension by causing injury of the lung vasculature, and examine the possible influences of TG on NO-release, CaN and ERK signaling pathways. MATERIALS AND METHODSMaterials TG (purity Ͼ93%), extracted from the leaf and stem of Panax ginseng C. A. MEYER, was presented by professor Rui Zhao (Beijing Naturally Occurring Drugs Research Institute, China), and was composed of Rb 1 (5.26%), Rg 1 (5.20%), Re (21.60%), Rd (13.65%), and other ginsenosides. MCT was purchased from Sigma Chemical Co. (U.S.A.). The antibodies against CnA, MKP-1, actin were obtained from Stressgen, Santa Cruz Company. Horseradish peroxidase conjugated goat anti-rabbit IgG were from Dako Cytomation Company. The reverse transcription kit and the primers o...

Ginseng protects rodent hearts from acute myocardial ischemia–reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism

“…Over the past decades, researchers have focused on defining the specific mechanism by which ginseng exerts its cardioprotective effects, especially its unique action in I/R injury (Liu et al, 2002;Qin et al, 2008). Although experimental studies have suggested that some ginsenosides play roles in cardioprotection against I/R injury, in clinical usage, ginseng is usually combined with other herbs.…”

“…Accumulated evidence has showed a connection between the action of ginseng and the MAPKs pathway. For example, compound K significantly repressed the PMA-mediated activation of p38 MAPK, Erk and JNK (Jung et al, 2006); total ginsenosides attenuated monocrotaline-induced right ventricle hypertrophy through suppressing activated Erk (Qin et al, 2008); ginsenoside Rd protected and rescued rat intestinal epithelial cells from irradiation-induced apoptosis through a pathway requiring inactivation of MEK (Tamura et al, 2008); ginsenoside Re reduces insulin resistance in 3T3-L1 adipocytes and high-fat diet rats through inhibition of JNK (Zhang et al, 2008). However, the role of the MAPKs pathway in ginseng's cardioprotective effects still remains unclear.…”

G.ALPHA.q-Protein Carboxyl Terminus Imitation Polypeptide (GCIP)-27 Inhibits Right Ventricular Hypertrophy Induced by Monocrotaline in Rats

“…It has been reported that the expressions of mRNA and/or protein of calcineurin (CaN) and the expression of mRNA of extracellular signal-regulated kinase-1 (ERK-1) from RVs in MCT-treated rats are significantly increased. 27,28) CaN and ERK signal pathways are known to be key mediators of cardiac hypertrophy. Therefore, whether GCIP-27 plays an important role on the repress of some key signal transduction pathways such as CaN signaling and ERK signaling in RV hypertrophy need more study in our future works.…”

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

“…4 Moreover, ginseng has been demonstrated to attenuate right and left ventricular hypertrophy in a number of experimental models. [5][6][7] Because the underlying basis for the antihypertrophic effect of ginseng is poorly understood, we studied the mechanisms for the antihypertrophic effect of ginseng using cultured ventricular myocytes and an in vivo model of heart failure secondary to chronic ischemia. The study centered primarily on the Na ϩ -H ϩ exchanger-1 isoform (NHE-1), which has been extensively shown to contribute to hypertrophy and heart failure.…”