Ginsenoside Rg1 inhibits rat left ventricular hypertrophy induced by abdominal aorta coarctation: Involvement of calcineurin and mitogen-activated protein kinase signalings

被引:33
作者
Deng, Jiang [1 ,2 ]
Lv, Xin-Tong [1 ]
Wu, Qin [1 ,2 ]
Huang, Xie-Nan [1 ,2 ]
机构
[1] Zunyi Med Coll, Dept Pharmacol, Zunyi 563000, Guizhou, Peoples R China
[2] Key Lab Basic Pharmacol Guizhou, Zunyi 563000, Peoples R China
关键词
Ginsenoside Rg(1); Left ventricular hypertrophy; Calcineurin; MAP kinase signaling; CARDIAC GENE-EXPRESSION; NECROSIS-FACTOR-ALPHA; CELLS; HYPERTENSION; PATHWAYS; MYOCYTES; RB-1; PROLIFERATION; PHARMACOLOGY; STIMULATION;
D O I
10.1016/j.ejphar.2009.01.048
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to inhibit proliferation of vascular smooth muscle cells induced by tumor necrosis factor-alpha. This study aims to investigate whether Rg(1) has protective effect on rat left ventricular hypertrophy and to probe its protective mechanisms. The rat left ventricular hypertrophy was induced by abdominal aorta coarctation and Rg(1) (3.75, 7.5 and 15 mg/kg/day) was given the day after surgery for 21 consecutive days. The left ventricular hypertrophy induced by abdominal aorta coarctation was evidenced by histopathology, electromicroscopy, and by determining the elevated left ventricular weight and the expression of atrial natriuretic peptide. Rg(1) significantly ameliorated left ventricular hypertrophy induced by abdominal aorta coarctation in a dose-dependent manner. To examine the mechanism of protection, the expressions of calcineurin, CnA (the catalytic subunit of calcineurin), extracellular signal-regulated kinase-1, and mitogen-activated protein (MAP) kinase phosphatase-1 were deter-mined at the transcript and protein levels. The abdominal aorta coarctation induced increases in calcineurin, CnA, and extracellular signal-regulated kinase-1 expressions were suppressed, but the expression of MAP kinase phosphatase-1 was increased by Rg(1). These results demonstrate that Rg(1) alleviates left ventricular hypertrophy induced by abdominal aorta coarctation, and the protection appears to be due, at least in part, to its inhibitory effects on calcineurin and MAP kinase signaling pathways. Crown Copyright (c) 2009 Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:42 / 47
页数:6
相关论文
共 31 条
[1]  
ANVERSA P, 1973, LAB INVEST, V29, P282
[2]   Ginseng pharmacology - Multiple constituents and multiple actions [J].
Attele, AS ;
Wu, JA ;
Yuan, CS .
BIOCHEMICAL PHARMACOLOGY, 1999, 58 (11) :1685-1693
[3]   Chronic NG-nitro-L-arginine methyl ester-induced hypertension -: Novel molecular adaptation to systolic load in absence of hypertrophy [J].
Bartunek, J ;
Weinberg, EO ;
Tajima, M ;
Rohrbach, S ;
Katz, SE ;
Douglas, PS ;
Lorell, BH .
CIRCULATION, 2000, 101 (04) :423-429
[4]   GENE-EXPRESSION IN CARDIAC-HYPERTROPHY [J].
BOHELER, KR ;
SCHWARTZ, K .
TRENDS IN CARDIOVASCULAR MEDICINE, 1992, 2 (05) :176-182
[5]   Calcineurin and hypertrophic heart disease: novel insights and remaining questions [J].
Bueno, OF ;
van Rooij, E ;
Molkentin, JD ;
Doevendans, PA ;
De Windt, LJ .
CARDIOVASCULAR RESEARCH, 2002, 53 (04) :806-821
[6]   Involvement of extracellular signal-regulated kinases 1/2 in cardiac hypertrophy and cell death [J].
Bueno, OF ;
Molkentin, JD .
CIRCULATION RESEARCH, 2002, 91 (09) :776-781
[7]   The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice [J].
Bueno, OF ;
De Windt, LJ ;
Tymitz, KM ;
Witt, SA ;
Kimball, TR ;
Klevitsky, R ;
Hewett, TE ;
Jones, SP ;
Lefer, DJ ;
Peng, CF ;
Kitsis, RN ;
Molkentin, JD .
EMBO JOURNAL, 2000, 19 (23) :6341-6350
[8]   TRANSCRIPTIONAL REGULATION DURING CARDIAC GROWTH AND DEVELOPMENT [J].
CHIEN, KR ;
ZHU, H ;
KNOWLTON, KU ;
MILLERHANCE, W ;
VANBILSEN, M ;
OBRIEN, TX ;
EVANS, SM .
ANNUAL REVIEW OF PHYSIOLOGY, 1993, 55 :77-95
[9]   REGULATION OF CARDIAC GENE-EXPRESSION DURING MYOCARDIAL GROWTH AND HYPERTROPHY - MOLECULAR STUDIES OF AN ADAPTIVE PHYSIOLOGICAL-RESPONSE [J].
CHIEN, KR ;
KNOWLTON, KU ;
ZHU, H ;
CHIEN, S .
FASEB JOURNAL, 1991, 5 (15) :3037-3046
[10]   Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress [J].
Esposito, G ;
Rapacciuolo, A ;
Prasad, SVN ;
Takaoka, H ;
Thomas, SA ;
Koch, WJ ;
Rockman, HA .
CIRCULATION, 2002, 105 (01) :85-92