ABSTRACT
Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor ß1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.
Subject(s)
Antioxidants/pharmacology , Drugs, Chinese Herbal/pharmacology , Forkhead Transcription Factors/metabolism , Hypertension, Renal/drug therapy , Nerve Tissue Proteins/metabolism , Oxidative Stress , Animals , Antioxidants/therapeutic use , Catalase/metabolism , Cytokines/metabolism , Drugs, Chinese Herbal/therapeutic use , Male , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Proteinuria/drug therapy , Rats , Rats, Inbred SHR , Rats, Wistar , Superoxide Dismutase/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Traditional Chinese medication (TCM) is increasingly used to treat cardiovascular disease (CVD) in China and some other Asian countries. However, therapeutic efficacy and adverse effects of TCM are difficult to evaluate because few large-scale, randomized controlled trials (RCTs) enrolling patients with CVD have been performed. In this Review, we critically examine the current evidence on the cardiovascular effects of TCM. We reviewed 68 RCTs that included a total of 16,171 patients. The methodological quality of the trials was generally low. Only three reports described adverse cardiovascular events specifically, although in most studies TCM was associated with significant improvements in surrogate end points for hypertension, coronary heart disease, cardiac arrhythmias, and heart failure. The risk of adverse effects was not increased compared with no intervention, placebo, or Western medications. However, whether TCM is effective in reducing the all-cause or cardiovascular mortality in patients with CVD remains unknown and must be tested in large-scale RCTs with adverse cardiovascular events as primary end points.
Subject(s)
Cardiovascular Diseases/drug therapy , Drugs, Chinese Herbal/therapeutic use , Arrhythmias, Cardiac/drug therapy , Coronary Disease/drug therapy , Heart Failure/drug therapy , Humans , Hypertension/drug therapy , Randomized Controlled Trials as Topic/methodsABSTRACT
BACKGROUND: It has been demonstrated that Tongxinluo (TXL), a traditional Chinese medicine compound, improves ischemic heart disease in animal models via vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The present study aimed to investigate whether TXL protects against pressure overload-induced heart failure in mice and explore the possible mechanism of action. METHODS AND RESULTS: Transverse aortic constriction (TAC) surgery was performed in mice to induce heart failure. Cardiac function was evaluated by echocardiography. Myocardial pathology was detected using hematoxylin and eosin or Masson trichrome staining. We investigated cardiomyocyte ultrastructure using transmission electron microscopy. Angiogenesis and oxidative stress levels were determined using CD31 and 8-hydroxydeoxyguanosine immunostaining and malondialdehyde assay, respectively. Fetal gene expression was measured using real-time PCR. Protein expression of VEGF, phosphorylated (p)-VEGF receptor 2 (VEGFR2), p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1 (HO-1), and NADPH oxidase 4 (Nox4) were measured with western blotting. Twelve-week low- and high-dose TXL treatment following TAC improved cardiac systolic and diastolic function and ameliorated left ventricular hypertrophy, fibrosis, and myocardial ultrastructure derangement. Importantly, TXL increased myocardial capillary density significantly and attenuated oxidative stress injury in failing hearts. Moreover, TXL upregulated cardiac nitrite content and the protein expression of VEGF, p-VEGFR2, p-PI3K, p-Akt, p-eNOS, and HO-1, but decreased Nox4 expression in mouse heart following TAC. CONCLUSION: Our findings indicate that TXL protects against pressure overload-induced heart failure in mice. Activation of the VEGF/Akt/eNOS signaling pathway might be involved in TXL improvement of the failing heart.
Subject(s)
Cardiotonic Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Heart Failure/drug therapy , Nitric Oxide Synthase Type III/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Animals , Capillaries/drug effects , Capillaries/pathology , Capillaries/physiopathology , Cardiomegaly/diagnostic imaging , Cardiomegaly/metabolism , Cardiomegaly/pathology , Cardiomegaly/physiopathology , Cardiotonic Agents/pharmacology , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Drugs, Chinese Herbal/pharmacology , Heart Failure/diagnostic imaging , Heart Failure/metabolism , Heart Failure/physiopathology , Heart Function Tests , Male , Mice, Inbred C57BL , Myocardium/pathology , Myocardium/ultrastructure , Oxidative Stress/drug effects , Signal Transduction/drug effects , UltrasonographyABSTRACT
Background. Myocardial infarction (MI) is a major cause of morbidity and mortality in the world. Tongxinluo (TXL) is a traditional Chinese compound prescription which has cardioprotective functions. The present study was aimed to determine the effect of TXL on postischemic cardiac dysfunction and cardiac remodeling and to elucidate the underlying mechanisms. Methods and Results. MI was performed by ligation of left anterior descending coronary artery (LAD) in male adult mice. Mice were randomly divided into four groups: (1) sham group (Sham); (2) MI-control group (Control); (3) MI-low dose TXL group (TXL-L); and (4) MI-high dose TXL (TXL-H) group. Compared with the control group, TXL treatment restored cardiac function, increased revascularization, attenuated cardiomyocyte apoptosis, and reduced interstitial fibrosis. TXL treatment increased the phosphorylation of Akt, extracellular signal regulated kinase (ERK), and endothelial nitric oxide synthase (eNOS); the expression of phosphatidylinositol3-kinase (PI3K), hypoxia-inducible factors 1 α (HIF-1 α ), and vascular endothelial growth factor (VEGF); and the DNA binding activity of HIF-1 α after MI. Conclusion. TXL may improve cardiac function and ameliorate cardiac remodeling by increasing neovascularization through enhancing the phosphorylation of Akt and ERK, the expression and activity of HIF-1 α , and the protein level of VEGF and p-eNOS.
ABSTRACT
OBJECTIVES: Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI. METHODS: A total of 120 male Wistar rats were randomized to 2 groups (n=60 each) for treatment: high-dose RGE (1.5 g·kg(-1)·day(-1) orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell-derived factor-1α (SDF-1α) were measured by immunohistochemistry, Western blot and quantitative PCR analysis. RESULTS: RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1α/CXCR4. In vitro, the effect of RGE on SDF-1α/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100. CONCLUSION: RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1α/CXCR4 cascade.
Subject(s)
Chemokine CXCL12/metabolism , Endothelial Cells/drug effects , Myocardial Infarction/prevention & control , Plant Extracts/pharmacology , Receptors, CXCR4/metabolism , Rehmannia/chemistry , Stem Cells/drug effects , AC133 Antigen , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Blotting, Western , Chemokine CXCL12/genetics , Endothelial Cells/metabolism , Gene Expression/drug effects , Glycoproteins/genetics , Glycoproteins/metabolism , Immunohistochemistry , Male , Myocardial Infarction/genetics , Myocardial Infarction/metabolism , Peptides/genetics , Peptides/metabolism , Phytotherapy , Random Allocation , Rats , Rats, Wistar , Receptors, CXCR4/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Signal Transduction/genetics , Stem Cells/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels.
Subject(s)
Doxycycline/pharmacology , Matrix Metalloproteinase Inhibitors/pharmacology , Matrix Metalloproteinases/chemistry , Plaque, Atherosclerotic/drug therapy , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Aorta, Abdominal/pathology , Doxycycline/blood , Immunohistochemistry/methods , Inflammation , Lipids/blood , Male , Plaque, Atherosclerotic/pathology , RNA, Messenger/metabolism , Rabbits , Ultrasonography/methodsABSTRACT
Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF(Met/Met) knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF(Met/Met) mice, but not in BDNF(+/)(-), mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF(Met/Met) mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF(+/)(-) mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF(Met) variant.
Subject(s)
Anxiety/genetics , Anxiety/rehabilitation , Brain-Derived Neurotrophic Factor/genetics , Methionine/genetics , Music Therapy/methods , Polymorphism, Single Nucleotide/genetics , Analysis of Variance , Animals , Anxiety/etiology , Anxiety/pathology , Brain/metabolism , Brain/pathology , Disease Models, Animal , Exploratory Behavior/physiology , Gene Expression Regulation/genetics , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Noise/adverse effects , RNA, Messenger/metabolism , Receptor, trkB/geneticsABSTRACT
This study was carried out to test the hypothesis that Tongxinluo (TXL) as a Chinese herbal medicine enhances stability of vulnerable plaque dose dependently via lipid-lowering and anti-inflammation effects, similar to a high-dose simvastatin therapy. After abdominal aortic balloon injury, 75 rabbits were fed a 1% cholesterol diet for 10 wk and were then divided into five groups for 8-wk treatment: control group, low-dose TXL group, moderate-dose TXL group, high-dose TXL group, and high-dose simvastatin group. At the end of week 16, an adenovirus containing p53 was injected into the abdominal aortic plaques. Two weeks later, plaque rupture was induced by pharmacological triggering. The incidence of plaque rupture in all treatment groups (14.3%, 7.1%, 7.7%, and 7.1%) was significantly lower than that in control group (73.3%; P>0.01). TXL dose-dependently lowered serum lipid levels and inhibited systemic inflammation. Corrected acoustic intensity and fibrous cap thickness of the aortic plaques were significantly increased, whereas plaque area, plaque burden, vulnerable index, and expression of oxidized low-density lipoprotein (ox-LDL) receptor 1, matrix metalloproteinase 1 (MMP-1), MMP-3, tissue inhibitor of MMP 1, and NF-kappaB in plaques were markedly reduced in all treatment groups when compared with the control group. Similar to high-dose simvastatin group, high-dose TXL group exhibited a low serum level of low-density lipoprotein cholesterol and ox-LDL, a low expression level of systemic and local inflammatory factors and a low plaque vulnerability index, with no differences in the incidence of plaque rupture among all treatment groups. TXL dose-dependently enhances the stability of vulnerable plaques and prevents plaques from rupture. Simvastatin and TXL offer similar protection in terms of lipid-lowering, anti-inflammation, and antioxidation effects.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Aortic Diseases/drug therapy , Aortic Rupture/prevention & control , Atherosclerosis/drug therapy , Drugs, Chinese Herbal/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Simvastatin/pharmacology , Animals , Aortic Diseases/etiology , Aortic Diseases/genetics , Aortic Diseases/metabolism , Aortic Diseases/pathology , Aortic Rupture/etiology , Aortic Rupture/genetics , Aortic Rupture/metabolism , Aortic Rupture/pathology , Atherosclerosis/etiology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Biomarkers/metabolism , Catheterization/adverse effects , Disease Models, Animal , Disease Progression , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Gene Transfer Techniques , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Hypercholesterolemia/pathology , Immunohistochemistry , Inflammation Mediators/metabolism , Lipids/blood , Male , RNA, Messenger/metabolism , Rabbits , Time Factors , Tumor Suppressor Protein p53/genetics , Ultrasonography, Doppler, Duplex , Ultrasonography, Interventional , Viper VenomsABSTRACT
UNLABELLED: RELEVANCE TO ETHNOPHARMACOLOGY: Tongxinluo capsule is a compound preparation formulated on the basis of the meridian theory of traditional Chinese medicine and is officially approved for the treatment of angina pectoris and ischemic stroke in China. OBJECTIVES: To test the hypothesis that the Chinese traditional medicine tongxinluo in capsule form has similar effects as simvastatin in lowering serum lipid levels and stabilizing vulnerable plaques. MATERIALS AND METHODS: Thirty New Zealand white rabbits underwent balloon-induced abdominal aortic endothelial injury and were fed a diet of 1% cholesterol for 8 weeks. The rabbits were then randomly divided into three groups (n=10 each) for daily doses of tongxinluo capsule (1 g/kg), simvastatin (5 mg/kg) or no drugs for 12 weeks. At the end of week 20, plaque rupture was induced by pharmacological triggering. Serological, ultrasonographic, pathologic, immunohistochemical, and gene expression studies were performed. RESULTS: The incidence of plaque rupture with tongxinluo and simvastatin treatment was significantly lower than that with control treatment (0% for both drug treatments vs. 56.0%; P<0.05). Values of serum lipid profile, inflammatory markers, and pathological and immunohistological assays were significantly improved in the tongxinluo- and simvastatin-treated groups than in the control group. The simvastatin-treated group showed lower serum lipid levels than the tongxinluo-treated group. CONCLUSIONS: Treatment with the Chinese medicine tongxinluo was as effective as simvastatin in lowering serum lipid levels, inhibiting plaque inflammation and preventing vulnerable plaques from rupture and may provide an alternative therapy for atherosclerosis.
Subject(s)
Aminoglycosides/blood , Anti-Inflammatory Agents/pharmacology , Cholesterol/blood , Drugs, Chinese Herbal/pharmacology , Endothelium, Vascular/drug effects , Hypolipidemic Agents/pharmacology , Magnoliopsida , Animals , Aorta, Abdominal/drug effects , Aorta, Abdominal/pathology , Cholesterol, LDL/blood , Diet , Disease Models, Animal , Endothelium, Vascular/pathology , Fidaxomicin , Rabbits , Random Allocation , Simvastatin/pharmacology , Triglycerides/blood , Tunica Intima/drug effects , Tunica Intima/pathologyABSTRACT
We randomly divided 100 unstable angina pectoris (UAP) patients into two groups: the trial group received Sulfotanshinone Sodium Injection (SSI) 60 mg combined with a loading dose of 300 mg aspirin and a maintenance dose of 100 mg of aspirin plus baseline therapy, and the control group received the same doses of aspirin and baseline therapy. 94 patients completed treatment. After 4 weeks' medication, the severity of angina pectoris improved in both groups, with a significant improvement in total effective rate in the trial group but no difference in the total effective rate of improvement seen on ECG. Compared with baseline level, FIB level after treatment decreased significantly in both groups but to a greater extent in the trial group. Similar changes in DD levels were observed in both groups. With a background of aspirin and baseline therapy, SSI can significantly attenuate angina pectoris attacks in patients with UAP which may be associated with the decreased level of FIB.
Subject(s)
Angina, Unstable/drug therapy , Anticoagulants/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Fibrinogen/metabolism , Phenanthrenes/administration & dosage , Salvia miltiorrhiza , Abietanes , Angina, Unstable/blood , Aspirin/administration & dosage , Dimerization , Female , Fibrinogen/chemistry , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle AgedABSTRACT
Hormone replacement therapy (HRT) can ameliorate lipid metabolism after menopause, but it is not suitable for long-term use because of serious side effects. Herba Epimedii is a widely used herbal medicine in many Asian countries, it potentially treats menopausal syndrome and its complications with few side effects and good curative effects. The study aimed to evaluate the effects of Herba Epimedii water extract on blood lipid and sex hormone levels. Ninety subjects were randomly divided into two groups: a trial group which received Herba Epimedii water extract and a control group which was administered an equal amount of water placebo. At the baseline and after 6 months of medication, serum estradiol (E(2)), progesterone (P), testosterone (T), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) concentrations were measured. The results indicated that Herba Epimedii water extract decreased the TC and TG levels (p < 0.01). Furthermore, Herba Epimedii water extract significantly increased the serum level of E(2) (p < 0.01) compared with the pre-treatment level. In conclusion, Herba Epimedii water extract produces its beneficial actions in postmenopausal women.
Subject(s)
Estrogens/blood , Lipid Metabolism/drug effects , Plant Extracts/pharmacology , Postmenopause , Adult , Aged , Double-Blind Method , Female , Humans , Middle Aged , Placebos , Plant Extracts/adverse effects , Progesterone/blood , Testosterone/blood , WaterABSTRACT
Unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) is associated with an increased risk of cardiac death and an efficacious drug with few side effects is necessary. The study aimed to evaluate the effects of Bulbus allii macrostemi (B. macrostemi) on UA/NSTEMI patients as well as to elucidate possible mechanisms. 79 patients were randomly divided into two groups: the trial group received B. macrostemi plus baseline therapy, the control group was given placebo plus baseline therapy. The trial lasted 8 weeks. The evaluation involved main clinical symptoms, changes of electrocardiogram and biochemical examination. After treatment, the trial group showed more significant improvement on clinical manifestation. The plasma oxidized low-density lipoprotein (ox-LDL) level decreased significantly in the trial group (p < 0.01); the plasminogen activator inhibitor-1 (PAI-1) level decreased in both groups and it decreased more significantly in the trial group (p < 0.01). In contrast, the activity of plasminogen (PLG) increased in both groups and the change was more marked in the trial group (p < 0.01). The results suggested that B. macrostemi combined with baseline therapy could improve clinical symptoms of UA/NSTEMI patients by decreasing the ox-LDL and PAI-1 levels and enhancing the activity of PLG.
Subject(s)
Angina, Unstable/drug therapy , Lipoproteins, LDL/metabolism , Myocardial Infarction/drug therapy , Onions/chemistry , Phytotherapy , Plasminogen/metabolism , Aged , Female , Humans , Lipoproteins, LDL/blood , Male , Medicine, Chinese Traditional , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Plasminogen Activator Inhibitor 1/metabolism , Treatment OutcomeABSTRACT
BACKGROUND: Tong-xin-luo capsule (TXL), used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats (SHR). METHODS: Sixteen eight-week-old SHRs were randomized into an SHR group (n = 8) and a TXL group (n = 8) that were given Tong-xin-luo capsule (1.5 mg x kg(-1) x d(-1)). Eight Wistar Kyoto (WKY) rats fed with 0.9% NaCl served as the control group (WKY group). Systolic blood pressure (BP), body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 (NF-kappaB P65) and peroxisome proliferators activated receptor gamma (PPAR-gamma) protein and phosphorylated inhibitor kappa alpha (IkappaBalpha) protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IkappaBalpha and NF-kappaB were measured by co-immunoprecipitation. PPAR-gamma mRNA, collagen I mRNA and collagen III mRNA were measured by real-time PCR. RESULTS: TXL inhibited NF-kappaB P65 expression and ventricular remodeling and suppressed the activation of NF-kappaB compared with the SHR group (P < 0.01, P < 0.05). TXL reduced IkappaBalpha phosphorylation, increased expression of PPAR-gamma protein and enhanced the physical interaction of the P65-P50 heterodimer with IkappaBalpha. The mRNA expression of PPAR-gamma was enhanced but the mRNA expression of collagen I mRNA and collagen I mRNA were suppressed by TXL. CONCLUSIONS: In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process of TXL increasing the expression of PPAR-gamma that could result in the inhibition of the activation of NF-kappaB.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Hypertension/drug therapy , NF-kappa B/antagonists & inhibitors , PPAR gamma/genetics , Ventricular Remodeling/drug effects , Animals , Collagen Type I/genetics , Collagen Type III/genetics , Hypertension/pathology , Male , RNA, Messenger/analysis , Rats , Rats, Inbred SHR , Ventricular Function, Left/drug effectsABSTRACT
Rhubarb has been used to decrease plasma cholesterol levels and reduce vascular endothelial cellular damage in recent years. However, it is not known whether reported lipid-lowering effects are associated with the improvement of endothelial function. This work aimed to elucidate the therapeutic effects of rhubarb on serum lipids and brachial artery endothelial function, as well as to investigate the relationship between them. One hundred and three patients with atherosclerosis were randomly divided into two groups: patients in the control and the trial group received a placebo and rhubarb, respectively, in addition to the 6 month baseline therapy. Serum lipids and brachial artery endothelial functions were measured in all patients before and after treatment. A total of 83 patients completed the 6-month follow-up protocol. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the trial group decreased significantly and LDL-C was significantly lower than that in the control group. Flow-mediated dilation (FMD) in the trial group was significantly higher after treatment in comparison to the baseline and to the control group. Improvement in FMD correlated with the decreased magnitude of TC and LDL-C levels. The results obtained appeared to confirm that rhubarb significantly improves endothelial function mainly due to lipid-lowering effects in patients with atherosclerosis.
Subject(s)
Atherosclerosis/drug therapy , Brachial Artery/physiopathology , Drugs, Chinese Herbal/therapeutic use , Endothelium, Vascular/physiopathology , Rheum , Aged , Atherosclerosis/blood , Atherosclerosis/physiopathology , Brachial Artery/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Drugs, Chinese Herbal/pharmacology , Endothelium, Vascular/drug effects , Female , Humans , Lipids/blood , Male , Middle Aged , Phytotherapy/methods , Vasodilation/drug effectsABSTRACT
OBJECTIVES: To investigate the effects of the Traditional Chinese Medicine (TCM) Quyu Xiaoban capsules (QYXB) on clinical outcomes and platelet activation and aggregation in patients with unstable angina pectoris (UAP) and phlegm and blood stasis syndrome. DESIGN: Ninety (90) UAP patients were randomly divided into two groups: the control group received a loading dose of 300 mg aspirin and a maintenance dose of 100 mg of aspirin plus baseline therapy for 4 weeks, and the trial group received the same doses of aspirin and baseline therapy plus QYXB for 4 weeks. The severity of anginal attacks, alterations of TCM symptoms and signs, and electrocardiographic (ECG) changes were observed in all patients before and after treatment. Plasma platelet aggregation (PAG) rate and P-selectin level were measured in all patients at baseline and at the end of the fourth week. RESULTS: After treatment for 4 weeks, both group of patients showed improvement in the severity of angina pectoris and TCM symptoms and signs, and there was a significant difference of the total effective rate in clinical improvement between the two groups, whereas no difference of the total effective rate in ECG improvement between the two groups was found. Compared with the baseline level, PAG rate in both groups decreased significantly at the end of the fourth week (63.74 +/- 11.18% versus 55.69 +/- 10.40 % in the control group, and 63.83 +/- 12.70% versus 50.04 +/- 8.91% in the trial group). Similar changes of P-selectin levels were observed in both groups (9.40 +/- 1.25 ng/mL versus 8.90 +/- 1.34 ng/mL in the control group and 9.56 +/- 1.16 ng/mL versus 7.80 +/- 0.98 ng/mL in the trial group). However, both PAG rate and P-selectin level decreased to a greater extent in the trial group than in the control group after treatment, and the difference between treatment was significant (both p<0.05). Nevertheless, these biochemical changes were too small to explain fully the beneficial clinical outcomes achieved by QYXB capsules. CONCLUSIONS: On the background of baseline and aspirin therapy, QYXB capsules significantly attenuated anginal attacks and improved TCM symptoms and signs in patients with UAP, and the exact mechanisms underlying these therapeutic effects remain to be explored.
Subject(s)
Angina, Unstable/drug therapy , Aspirin/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation , Adult , Angina, Unstable/prevention & control , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Electrocardiography , Female , Humans , Male , Middle Aged , P-Selectin/blood , Platelet Aggregation/drug effects , Treatment OutcomeABSTRACT
OBJECTIVES: To investigate the effects of the Traditional Chinese Medicine (TCM) Quyu Xiaoban capsules (QYXB) on clinical outcomes and platelet activation and aggregation in patients with unstable angina pectoris (UAP) and phlegm and blood stasis syndrome. DESIGN: Ninety patients with UAP were randomly divided into two groups: a control group that received a loading dose of 300 mg aspirin and a maintenance dose of 100 mg of aspirin plus baseline therapy for 4 weeks, and a trial group that received the same doses of aspirin and baseline therapy plus QYXB for 4 weeks. The severity of anginal attacks, alterations of TCM symptoms and signs, and electrocardiographic (ECG) changes were assessed in all patients before and after treatment. The plasma platelet aggregation (PAG) rate and P-selectin level were measured in all patients at baseline and at the end of the fourth week of treatment. RESULTS: After treatment for 4 weeks, both group of patients showed improvement in the severity of angina pectoris and TCM symptoms and signs, but there was a significant difference in the two groups' rates of clinical improvement, whereas the rate of ECG improvement of the two groups showed no difference. As compared with the baseline value, the PAG rate in both groups decreased significantly at the end of the fourth week (63.74 +/- 11.18% vs. 55.69 +/- 10.40% in the control group, and 63.83 +/- 12.70% vs. 50.04 +/- 8.91% in the trial group). Similar changes in P-selectin levels were observed in the two groups (9.40 +/- 1.25 ng/mL vs. 8.90 +/- 1.34 ng/mL in the control group, and 9.56 +/- 1.16 ng/mL vs. 7.80 +/- 0.98 ng/mL in the trial group). However, both the PAG rate and P-selectin level decreased to a greater extent in the trial group than in the control group after treatment, and the difference between the two groups was significant (both p < 0.05). Nevertheless, these biochemical changes were too small to fully explain the beneficial clinical outcomes achieved with QYXB capsules. CONCLUSIONS: In comparison with both the respective baseline values and with aspirin therapy, QYXB capsules significantly attenuated anginal attacks and improved TCM symptoms and signs in patients with UAP. The exact mechanisms underlying these therapeutic effects remain to be explored.
Subject(s)
Angina, Unstable/drug therapy , Aspirin/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation/drug effects , Angina, Unstable/prevention & control , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Electrocardiography , Female , Humans , Male , Middle Aged , P-Selectin/blood , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the therapeutic effects of Quyu Xiaoban Capsule (QYXBC) on endothelial dependent vascular relaxation (EDVR) function in patients with atherosclerosis (AS) with ultrasonic technique. METHODS: Tested were the endothelial function and blood lipids of 42 patients with AS in the treated group and 30 healthy volunteers in the control group. And re-examination of these parameters was carried out on the AS patients after they had been treated with QYXBC for 10 months. RESULTS: Before treatment, the reactive hyperemia induced changes in artery diameter in the treated group was significantly lower than that in the control group (P < 0.01), while insignificant difference was found between the two groups in response to nitroglycerin. In the treated group after treatment, with D%-R improved significantly (P < 0.01), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) decreased by 16.3%, 5.6%, 10.2% respectively and high-density lipoprotein cholesterol (HDL-C) increased by 7.5%. EDVR was correlated negatively with the serum TC, LDL-C concentrations and the baseline brachial diameter (D(0)) (r = -0.41, -0.66, -0.59, respectively, all P < 0.01), but correlated positively with HDL-C (r = 0.62, P < 0.05). The ameliorative extent of EDVR was correlated positively to the decreased magnitude of TC and LDL-C concentrations (r = 0.67, 0.59, both P < 0.01). CONCLUSION: QYXBC can lower the level of blood lipids and improve significantly EDVR function.
Subject(s)
Carotid Artery Diseases/drug therapy , Drugs, Chinese Herbal/administration & dosage , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Phytotherapy , Adult , Aged , Brachial Artery/physiology , Carotid Artery Diseases/diagnostic imaging , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Drugs, Chinese Herbal/adverse effects , Female , Humans , Male , Middle Aged , Ultrasonography , Vasodilation/drug effectsABSTRACT
OBJECTIVE: To observe the effect of daidzein on serum inflammatory factors of senile patients with coronary heart disease (CHD). METHODS: Forty senile patients with CHD were randomly assigned into the control group and the daidzein group, 20 in each group. Patients in both groups were treated with conventional medicine, while those in the daidzein group were given daidzein Tablets additionally for 6 weeks. The levels of resting heart rate (RHR), blood pressure (BP), fasting plasma glucose (FPG), blood lipids and inflammatory factors, including hsCRP, IL-6 and TNF-alpha, were measured before and after treatment. RESULTS: In the control group, the levels of RHR, BP and hsCRP changed after conventional medicinal treatment (P < 0.05 or P < 0.01) but other parameters unchanged (P > 0.05). While in the daidzein group, all the parameters measured were decreased in different degrees after 6 weeks treatment (P < 0.05 or P < 0.01), and also showed significant difference as compared with those in the control group respectively (P < 0.05 or P < 0.01). CONCLUSION: Daidzein can effectively decrease the levels serum inflammatory factors in senile patients with CHD, the fact proved that isoflavone has anti-inflammatory effect in patients with coronary atherosclerosis.