ABSTRACT
BACKGROUND: Leonurus heterophyllus sweet has been suggested to have cardioprotective effects against heart diseases, including ischemic diseases and ventricular remodeling. However, the active ingredients of the herb and the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of stachydrine (STA), a major constituent of Leonurus heterophyllus sweet, on norepinephrine (NE) induced hypertrophy and the changes of calcium transients in neonatal rat cardiomyocytes. METHODS: Ventricular myocytes from 1-day-old Wistar rats were isolated and cultured in DMEM/F12 with 1 µmol/L norepinephrine in the presence or absence of 10 µmol/L STA for 72 h. Cardiomyocytes hypertrophy was evaluated by cell surface area, total protein/DNA content, ß/α-MHC mRNA ratio. While calcium handling function was evaluated by Ca2+-transient amplitude and decay, SERCA2a activity and expression, PLN expression and phosphorylation. ß1-adrenergic receptor system activation was evaluated by the content of cAMP and the activation of PKA. RESULTS: NE treatment increases the cell surface area, protein synthesis, the expression level of ß-MHC and ß/α-MHC ratio. These effects were attenuated by STA. NE-induced hypertrophy was associated with increased Ca2+-transient amplitude, accelerated decay of the Ca2+-transient, increased phospholamban expression, hyper-phosphorylation at both the serine-16 and threonine-17 residues, increased intracellular cAMP level, and PKA overactivation. All of which were significantly inhibited by STA. CONCLUSION: These data suggest that STA attenuates norepinephrine-induced cardiomyocyte hypertrophy and has potential protective effects against ß-adrenergic receptor induced Ca2+ mishandling.
Subject(s)
Calcium/metabolism , Heart Diseases/drug therapy , Leonurus/chemistry , Myocytes, Cardiac/drug effects , Norepinephrine/metabolism , Plant Extracts/pharmacology , Proline/analogs & derivatives , Animals , Animals, Newborn , Heart/drug effects , Heart Diseases/metabolism , Heart Diseases/pathology , Hypertrophy/drug therapy , Male , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Norepinephrine/adverse effects , Phosphorylation , Phytotherapy , Plant Extracts/therapeutic use , Proline/pharmacology , Proline/therapeutic use , Rats, Wistar , Signal Transduction/drug effects , Ventricular Remodeling/drug effectsABSTRACT
UNLABELLED: objective: To investigate effects of buyang huanwu decoction (BYHWD) on the rats' myocardial hypertrophic model induced by abdominal aortic constriction, and to clarify the molecular regulatory mechanisms for sarcoplasmic reticulum calcium uptake. METHODS: Hypertrophic myocardium rat model was induced by abdominal aorta constriction (AAC). Four weeks after modeling, rats were randomly divided into the sham-operation group (Group S), the AAC model group (Group M), the Enalapril group (Group E), and the BYHWD treatment group (Group BYHWD), respectively. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), + dp/dtmax,-dp/dtmax, cardiac output (CO), heart mass index (HMI), and left ventricular mass index (LVMI) were observed in each group after 12-week medication. The serum contents of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were detected using ELISA. The SERCA2a activity, the ex- pressions of SERCA2a, phospholamban (PLN), and PLN phosphorylation were observed finally. RESULTS: Compared with Group S, LVSP and LVEDP significantly increased,-dp/dtmax and CO obviously decreased, the myocardial tissue was obviously thickened, the serum contents of ANP and BNP increased, the activity and expression of SERCA2a decreased, the SERCA2a/PLN ratio and PLN phosphorylation degree decreased in Group M (all P <0.05). Compared with Group M, LVEDP obviously decreased, -dp/dtmax and CO obviously increased, the hypertrophy myocardial tissue was obviously lessened, the serum contents of ANP and BNP decreased, the activity of SERCA2a increased, the relative expression contents of SERCA2a, Ser16, and Thrl7 were elevated in Group BYHWD (all P <0.05). BYHWD had significant roles in elevating the SERCA2a/PLN ratio and PLN phosphorylation degree (P <0.05). CONCLUSION: BYHWD could significantly improve hemodynamics of heart failure rats, elevate CO, lessen cardiac hypertrophy, and improve the capabilities for sarcoplasmic reticulum calcium uptake.
Subject(s)
Calcium/metabolism , Constriction, Pathologic/metabolism , Drugs, Chinese Herbal/pharmacology , Sarcoplasmic Reticulum/metabolism , Animals , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/pathology , Hypertrophy, Left Ventricular/metabolism , Hypertrophy, Left Ventricular/pathology , Male , Myocardium/pathology , Rats , Rats, WistarABSTRACT
OBJECTIVE: To investigate the effects of Leonurus stachydrine on myocardial cell hypertrophy induced by angiotensin II in rats. METHODS: Myocardial cells of neonatal rats were incubated with angiotensin II for 48 hours to establish myocardial cell hypertrophy models. The cell surface area and protein/DNA ratio were detected as index for hypertrophy of myocardial cells. ROS positive myocardial cell were counted by means of flow cytometry, the expression of p-IkappaB (ser32) protein in the cytosol and NF-kappaB (p65) protein in the nucleus were also detected by Western blot. RESULTS: Various concentrations of stachydrine intervention (10(-6) - 10(-4) mol/L) showed better anti-hypertrophic effect and decreased the number of ROS positive myocardial cell (P<0.05). Meanwhile, intervention of stachydrine significantly suppressed the level of p-IkappaB (ser32) protein in the cytosol and NF-kappaB (p65) protein in the nucleus (P<0.05). CONCLUSION: Stachydrine can inhibit the NF-kappaB signal pathway, and this may be ralated to the mechanism of anti-hypertrophic.
