Active components from Radix Scrophulariae inhibits the ventricular remodeling induced by hypertension in rats.

BACKGROUND: In the previous study, active extract of Radix Scrophularia (ACRS) demonstrated beneficial effects on ventricular remodeling induced by coronary artery ligation and lowered blood pressure in rats. And ACRS also exhibited the effect on lowering the blood pressure in spontaneously hypertensive rats (SHRs). The aim of this study is to explore the effects of ACRS on ventricular remodeling in SHRs and underlying mechanisms. RESULTS: ACRS significantly lowered the blood pressure, decreased the heart mass indexes, inhibited the deposition of perivascular and interstitial, attenuated the accumulation of types I and III collagen, reduced the tissue angiotensin II, serum norepinephrine and tumor necrosis factor-α concentrations. The underlying mechanisms may be related to downregulating the mRNA expressions of collagen type I, transforming growth factor-ß1 and angiotensin converting enzyme, suppressing the phosphorylation of extracellular signal regulated kinase 1/2, c-Jun N-terminal kinase (JNK/SAPK) and p38 mitogen-activated protein kinases (p38 MAPK). CONCLUSION: Continuous treatment of SHRs with ACRS for 21 weeks reduced blood pressure, myocardial hypertrophy and the amount of interstitial and perivascular collagen, which indicated that ACRS could prevent hypertensive ventricular remodeling. This can be attributed to suppression of the sympathetic nervous and renin angiotensin aldosterone system through the inhibition of ERK 1/2, JNK and p38 MAPK pathways.

Protective and Therapeutic Effects of Chinese Medicine Formula Jiajian Yunvjian on Experimental Cardiac Remodeling after Myocardial Infarction Induced by Coronary Artery Ligation.

Introduction. This study was designed to explore the effect and mechanism of a classic Chinese medicine formula Jiajian Yunvjian (JJYNJ) on cardiac remodeling. Cardiac remodeling after myocardial infarction (MI) model was achieved by coronary artery ligation (CAL). Methodology. When dosed orally once daily, the effects of JJYNJ on hemodynamics, left ventricular weight index (LVWI), heart weight index (HWI), concentration, and gene expression of neuroendocrine factors as well as the histomorphological observation were determined. Results. After 4 weeks, mild cardiac remodeling in CAL group was characterized compared with sham group, but after 4 weeks of treatment of JJYNJ, hemodynamics improved, HWI reduced, and circulating angiotensin II (Ang II), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), and hydroxyproline (Hyp) concentrations as well as Ang II receptor type 1 (AT1R) mRNA, transforming growth factor ß 1 (TGF-ß 1) mRNA, and TNF-α mRNA levels in myocardium were lower than in CAL group. Decreased plasma aldosterone (ALD) concentration, cross-sectional area of cardiomyocyte, collagen volume fraction (CVF), collagen types I and III, perivascular collagen area (PVCA), and upregulated nitric oxide (NO) levels were observed at the same time. Conclusions. These findings suggest that JJYNJ may have a protective and therapeutic function on cardiac remodeling related to MI.

The effect of angoroside C on pressure overload-induced ventricular remodeling in rats.

BACKGROUND: Our previous study reveals that total rough extract of Radix Scrophulariae has a beneficial effect on ventricular remodeling. HYPOTHESIS: After carrying out a series of preliminary experiments, we speculated that angoroside C may be the effective agent. STUDY DESIGN: After oral administration, the effect of angoroside C on ventricular remodeling was evaluated by using a pressure-overloaded rat model, some related indexes were detected in vivo. METHODS: A model of pressure overloaded ventricular remodeling was produced by abdominal aortic constriction (AAC) in rats. The sham-operated rats underwent an identical surgical procedure except for AAC. AAC rats were randomly divided into five groups: model control group, three angoroside C treated groups (7.5, 15 and 30 mg·kg(-1)) and captopril treated group (40 mg·kg(-1)). The rats were orally administered with the corresponding drugs or drinking water for 4 weeks. The levels of blood pressure (BP), left ventricular weight index (LVWI) and heart weight index (HWI) were detected. Myocardium tissue was stained with hematoxylin and eosin or picric acid/sirius red for cardiomyocyte cross-section area or collagen content measurements respectively. The concentrations of angiotensin Ⅱ (Ang Ⅱ), hydroxyproline (Hyp), matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in myocardium or serum were determined. Real-time RT-PCR was performed to detect the mRNA expressions of endothelin 1 (ET-1), transforming growth factor ß1 (TGF-ß1). RESULTS: Angoroside C significantly reduced the BP, LVWI and HWI, decreased the content of Ang Ⅱ, Hyp, diminished cross sectional area of cardiomyocytes and ameliorated collagen deposition. Additionally, it markedly reduced collagen I and III expressions and regulated matrix metalloproteinase-2, 9 and inhibitors of metalloproteinase expressions. Angoroside C also down regulated the gene expressions of ET-1 and TGF-ß1mRNA in myocardium. CONCLUSION: Angoroside C has beneficial effects against ventricular remodeling. The mechanism is likely to be related to decreasing the level of Ang Ⅱ, attenuating the mRNA expressions of ET-1 and TGF-ß1.

Effect of gentiopicroside on experimental acute pancreatitis induced by retrograde injection of sodium taurocholate into the biliopancreatic duct in rats.

Gentiopicroside (otherwise known as Gentiopicrin), one of the main active ingredients from the traditional Chinese herb medicine Gentiana manshurica Kitag, presents the effect of attenuating acute pancreatitis in rats. The experimental acute pancreatitis was made by retrograde injection of sodium taurocholate into the biliopancreatic duct in rats. Gentiopicroside was given orally and it markedly reduced the pancreatitis-evoked increase of serum amylase and lipase activity, decreased the pancreas mass/body mass index, tissue water content, TNF-α and IL-1ß concentrations, and attenuated the histopathological changes and NF-κB p65 protein expression in pancreatic tissue. The results indicate that the function of gentiopicroside on acute pancreatitis may be related to inhibiting the release of inflammatory mediators and NF-κB p65 protein expression.

[Effect of Chrysanthemum indicum on ventricular remodeling in rats].

OBJECTIVE: To explore the effects and mechanism of Chrysanthemum indicum on experimental ventricular remodeling induced by isoprenaline (ISO) and L-thyroxine (L-Thy). METHODS: The ventricular remodeling of mice were induced by subcutaneous injection of ISO with the dosage of 2 mg/kg daily for 7 d and the rats with L-Thy intraperitoneally with the dosage of 0.25 mg/kg daily for 9 d. After 7 days' treatment, the cardiac index and the Ang II content in myocardium of mice were measured. After 9 days' treatment, the ratios of LVW/BW, HW/BW of rats were calculated, the Ang II content in heart tissue and the ALD, TNF-alpha concentration in serun were determined by radioimmunoassay, the Hydroxy proline (Hyp) content in heart tissue were measured by hydrolysis method. RESULTS: After 7 - 9 days of treatment, Chrysanthemum indicum significantly reduced the left ventricular weight index and heart weight index in mice and rats with myocardial hypertrophy, decreased the content of Ang II in ventricular tissue in mice and rats, and reduced the ALD, TNF-alpha concentration in serum and the Hyp content in ventricular tissue in rats (P < 0.05). CONCLUSION: Chrysanthemum indicum can significantly attenuate the experimental ventricular remodeling; the mechanism may be related with restricting the activity of the sympathetic nervous system and decreasing the levels of Ang II, ALD and TNF-alpha.

Effects of Chinese herb medicine Radix Scrophulariae on ventricular remodeling.

The effects and mechanism of the extract of Radix Scrophulariae (ERS), a traditional Chinese herb, on experimental ventricular remodeling in rats was studied. Rats were separated randomly into 5 groups: sham, model, captopril (40 mg x kg(-1)) and ERS (8, 16 g x kg(-1)). The experimental ventricular remodeling was induced with ligating the left anterior descending branch of the coronary artery of the rats. The sham group was conducted the same procedure without ligation. After 4 weeks treatment with intragastric administration of the corresponding drugs, the left ventricular weight index (LVWI) and heart weight index (HWI) were determined. The concentrations of angiotensin II (Ang II) and hydroxyproline (Hyp) in myocardium were detected. Myocardium tissue was stained with HE and picric acid/Sirius red for cardiocyte cross-section area and collagen content measurements. Real-time RT-PCR was used to detect the gene expressions of AT1R, TNF-alpha and TGF-beta1 mRNA. ERS could significantly reduce the LVWI, HWI, decrease the content of Ang II, Hyp, diminish cardiocyte cross-section area and ameliorate collagen deposition. In addition, ERS could down regulate the gene expressions of AT1R, TNF-alpha and TGF-beta1 mRNA in myocardium. ERS has beneficial effect against ventricular remodeling. The mechanism may be related to decreasing the level of Ang II and cardiac fibrosis, modulating some gene expressions associated with cardiac hypertrophy.

Effect of sodium houttuyfonate on inhibiting ventricular remodeling induced by abdominal aortic banding in rats.

Ventricular remodeling is an independent risk factor for many cardiovascular events. Inhibiting ventricular remodeling early may be an effective way to postpone heart failure for patients with cardiovascular illness. The study was designed to examine the effect of sodium houttuyfonate on ventricular remodeling induced by pressure overload in rats, as well as to explore the mechanisms involved. The model rats in which ventricular remodeling was induced abdominal aortic banding (AAB) were randomly divided into 4 groups: AAB control, AAB plus captopril (40 mg/kg), AAB plus low dose of sodium houttuyfonate (50 mg/kg), and AAB plus high dose of sodium houttuyfonate (100 mg/kg). One month after operation, hemodynamic parameters, heart mass indexes, size of cardiomyocytes, myocardial collagen volume, angiotensin II content in ventricular tissue, and serum concentrations of aldosterone and tumor necrosis factor (TNF)-alpha were evaluated. Sodium houttuyfonate significantly reduced heart mass indexes, the size of cardiomyocytes, and the myocardial collagen volume and decreased the levels of angiotensin II, aldosterone, and TNF-alpha. At the high dose, it decreased blood pressure and heart rate. In conclusion, sodium houttuyfonate attenuates ventricular remodeling induced by pressure overload in rats. The beneficial effects are in part associated with its alleviating the activation of renin-angiotensin-aldosterone system and decreasing the TNF-alpha level. Furthermore, its function seems to correlate with reduced blood pressure and heart rate.

Effects of polydatin on attenuating ventricular remodeling in isoproterenol-induced mouse and pressure-overload rat models.

The study was designed to examine the effects of polydatin on ventricular remodeling induced by isoproterenol in mice and by abdominal aortic banding in rats. Polydatin reduced cardiac weight indexes in mice and rats, lowered the contents of cyclic AMP and angiotensin II in mice. It also decreased the size of cardiomyocyte, the levels of aldosterone, tumor necrosis factor-α, angiotensin II and endothelin-1, reduced ventricular collagen volume and decreased blood pressure in rats. The results demonstrate that polydatin has the beneficial effects on attenuating ventricular remodeling, which are associated with its inhibiting the activation of neurohormone, especially in rennin-angiotensin-aldosterone system.

[Progress in treatment of chronic heart failure in Western medicine and treatment strategies in traditional Chinese medicine].

The concept of modern medicine in treating chronic heart failure (CHF) has changed markedly in recent years. To improve the quality of life and prolong life, the treatment goal is no longer just temporary improvement of symptoms, more importantly, is to prevent and delay the occurrence and development of ventricular remodeling. Long-term chronic over-activation of sympathetic system, renin-angiotensin-aldosterone system and other neuroendocrine factors promotes myocardial remodeling, increases myocardial injury and deteriorates cardiac function. Despite short-term use can significantly improve the blood flow dynamics, long-term use of beta-adrenergic receptor stimulators and phosphodiesterase inhibitors does not prolong life, but increases the rate of sudden death caused by cardiac arrhythmia. Angiotensin converting enzyme inhibitors and beta-blockers have become the preferred drugs in treating chronic heart failure. In fact, after long-term use, beta-blockers can significantly improve ventricular remodeling, enhance ventricular function and reduce the incidence of sudden death of patients with CHF. In traditional Chinese medicine practice, short-term use of drugs for warming yang and reinforcing qi can improve symptoms of CHF, but long-term use may have adverse effects, for these medicines can stimulate sympathetic system. Early treatment with medicines of cold and cool property may be more favorable to patients with CHF, except the advanced patients who need special intervention. Eliminating heat and nourishing yin may play more active role in controlling the occurrence and development of CHF. Drugs with good efficacy and value in treating CHF may be developed from the Chinese herbal medicines with eliminating heat and nourishing yin property.

Effect of sodium houttuyfonate on myocardial hypertrophy in mice and rats.

OBJECTIVES: The aim of the study was to determine the effect of sodium houttuyfonate on myocardial hypertrophy and its mechanism of action in mice and rats. METHODS: A mouse model of myocardial hypertrophy was established by subcutaneous injection with isoproterenol. Mice were randomly divided into five groups: normal control; isoproterenol control; isoproterenol plus metoprolol; isoproterenol plus low- and high-dose sodium houttuyfonate. A rat model of myocardial hypertrophy was established by intraperitoneal injection with L-thyroxine. Rats were randomly divided into five groups: normal control; L-thyroxine control; L-thyroxine plus captopril; L-thyroxine plus low- and high-dose sodium houttuyfonate. At the end of the experiments, the left ventricular weight index and heart weight index were determined in mice and rats, the size of cardiomyocytes was measured in rats and the concentrations of cAMP in plasma and angiotensin II in ventricular tissue of mice were detected by radioimmunoassay. The endothelin-1 concentration was measured by radioimmunoassay and the hydroxyproline content was measured by a digestive method in ventricular tissue of rats. KEY FINDINGS: After 7-9 days of treatment, sodium houttuyfonate significantly reduced the left ventricular weight index and heart weight index in mice and rats with myocardial hypertrophy, decreased the size of cardiomyocytes in rats, and reduced the content of cAMP and angiotensin II in mice with myocardial hypertrophy. It also decreased the endothelin-1 concentration and the hydroxyproline content in ventricular tissue in rats. CONCLUSIONS: Sodium houttuyfonate can inhibit myocardial hypertrophy in mouse and rat models by restricting the activity of the sympathetic nervous system and decreasing the levels of angiotensin II and endothelin-1 in ventricular tissue.

[The study of Xuanshen on ventricular remodeling and cardiac endothelin-1 expression in rats treated with pressure-overload].

OBJECTIVE: To investigate the influence of Xuanshen on cardiac endothelin-1 expression, ventricular remodeling and its mechanism in rats treated with pressure-overload. METHODS: The ventricular remodeling model was induced by abdominal aortic stenosis in rats. Meanwhile, sham-operated rats were established as the control group. 8 weeks after drug interference, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular weight and heart weight index (LVWI and HWI), the activity of superoxide dismutase (SOD), cardiac endothelin-1 concentration and its gene expression were determined. RESULTS: Compared with those of sham-operated rats, the HR, SBP, DBP, LVWI and HWI of the model rats were increased significantly. The activity of SOD decreased, the concentration of cardiac endothelin-1 and its gene expression increased. In groups treated with Xuanshen, the HR, SBP, DBP, LVWI and HWI declined and the activity of SOD was improved. Moreover, the concentration of cardiac endothelin-1 and its gene expression decreased. CONCLUSION: Pressure-overload may induce oxidative stress and over-expression of cardiac endothelin-1. Xuanshen can inhibit ventricular remodeling. The mechanism may be related to the inhibition of oxidative stress and down regulation of endothelin-1 expression.

[Influence of Tinglizi on collagen volume fraction and perivascular collagen area in left ventricle tissue of cardiac hypertrophy induced by abdominal aortic banding in rats].

OBJECTIVE: To evaluate the influence of Tinglizi on collagen volume fraction (CVF) and perivascular collagen volume area (PVCA ) in left ventricle tissue of cardiac hypertrophy induced by abdominal aortic banding in rats. METHOD: Ventricular remodeling was induced by abdominal aortic banding (AAB) in rats. After 30 day treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP); heart rate (HR) were measured. The histological assay consisted of the HE stain for determining the myo-cardium cell cross section and collagen stain (Van Gieson' method) for determining collagen content, including collagen volume fracton (CVF) and perivascular collagen volume area (PVCA). RESULT: The experimental data demonstrated that Tinglizi decreased SBP, DBP, HR and could significantly reduce the total collagen content (CVF, PVCA) and lessen the myocardium cell cross section (P < 0.05). CONCLUSION: Tinglizi may decrease the total collagen content of ventricle and attenuate the ventricular remodeling induced by abdominal aortic banding.

[Comparative study of Scrophulariae and Aconite in inhibiting myocardial hypertrophy in rats and mice].

OBJECTIVE: To explore the effects of Scrophulariae of cold nature and Aconite of hot nature on myocardial hypertrophy and neuroendocrine factors in rats and mice. METHODS: A mouse model of myocardial hypertrophy was established by hypodermic injection of isoproterenol. Sixty myocardial hypertrophy mice were randomly divided into five groups: normal control group, untreated group, metoprolol-treated group, Scrophulariae-treated group and Aconite-treated group. A rat model of myocardial hypertrophy was established by peritoneal injection of L-thyroxin. Fifty rats were randomly divided into five groups: normal control group, untreated group, captopril-treated group, Scrophulariae-treated group and Aconite-treated group. After 7-9 days of treatment with intragastric administration of the corresponding drugs, the effects of Scrophulariae and Aconite on left ventricular weight index (LVWI) and heart weight index (HWI) were determined. The concentrations of cyclic adenosine monophosphate (cAMP) in plasma and angiotensin II (Ang II) in myocardium were detected through radio-immunity method. Cardiocyte cross-section area was determined by using HE staining. RESULTS: Scrophulariae of cold nature could significantly reduce the LVWI, HWI and cardiocyte cross-section area, and could decrease the content of cAMP and Ang II. However, Aconite had no such effects. CONCLUSION: Scrophulariae of cold nature can inhibit myocardial hypertrophy through restraining the activity of sympathetic nervous system and decreasing the level of Ang II. The inhibition of Aconite of hot nature on cardiac hypertrophy is not significant.

[Semen descurainiae inhibits CYP11B1, CYP11B2 and TGF-beta1 mRNA expression in left ventricular].

OBJECTIVE: To investigate the effects of Semen descurainiae and Captopril on CYP11B1, CYP11B2 and TGF-beta1 mRNA expression of heart tissue in rats treated with Abdominal Aortic Banding. METHODS: Ventricular remodeling was induced by abdominal aortic banding (AAB) in rats. After 30 days' treatment, the ratios of LVW/BW (left ventricle weight/body weight), HW/BW (heart weight/body weight) were calculated; Then the CYP11B, CYP11B2 and TGF-beta1 mRNA expression of left ventricle were detected by Real-time PCR, respectively. RESULTS: The experimental data demonstrated that Semen descurainiae decreased the indexes of LVW/BW and HW/BW, down-regulated CYP11B, CYP11B2 and TGF-beta1 mRNA expression in left ventricle (P<0.05). CONCLUSION: Semen desceurainiae can significantly inhibit the experimental ventricular remodeling; the mechanism is related to its ability to attenuate the mRNA expression of CYP11B1, CYP11B2 and TGF-beta1 in left ventricle. The inhibition of aldosterone key gene expression by Semen descurainiae may contribute to its effect on restraint cardiac remodeling.