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OBJECTIVE@#To investigate the effect of Chinese compound Shensong Yangxin Capsule ( , SSYX) on myocardial microcirculation in myocardial-infarcted rabbits.@*METHODS@#Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. Thirty rabbits were randomly divided into the control group, the MI group (model), and the MI treated with SSYX group (MI+SSYX) by a random number table method. After 4 weeks of administration, low-energy real-time myocardial contrast echocardiography (RT-MCE) was conducted to assess the microcirculatory perfusion. Immunofluorescence double staining was used to detect the capillary density. The endothelial ultrastructure was observed with a transmission electron microscope. The mRNA expression levels of vascular endothelial growth factor (VEGF), endothelin 1 (ET-1), prostaglandin I2 (PGI2) and endothelial nitric oxide synthase (eNOS) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). The plasmic levels of ET-1, thromboxane A2 (TXA2), nitric oxide (NO) and von willebrand factor (vWF) were examined with enzyme-linked immunosorbent assays (ELISA).@*RESULTS@#SSYX significantly improved the myocardial blood volume, myocardial micro bubble velocity, and myocardial inflow according to the examination of RT-MCE, and it visibly ameliorated the capillary endothelial structure. Furthermore, compared with the MI group, the plasma levels of TXA2, ET-1 and vWF contents significantly decreased in the MI+SSYX group, and the ET-1 mRNA expression levels of myocardium in the border zone significantly decreased, and the VEGF, PGI2 and eNOS mRNA expression levels significantly increased (all P<0.05).@*CONCLUSIONS@#SSYX has favorable advantages in ameliorating the impaired myocardial microcirculation following MI. The mechanisms of the effect are related to the ability of SSYX in balancing the endothelial-derived vasodilators and vasoconstrictors, and up-regulating the expression of VEGF and eNOS.
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Objective: To investigate the chemical composition of Shensong Yangxin Capsule, a novel ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to establish a method that could identify the ingredients systematically and rapidly. Methods: The information of accurate mass and multistage fragment ions was obtained by the novel UHPLC-Q-Orbitrap technology. Chemical constituents were characterized by comparing the relative retention time and the mass data of the reference substance, meanwhile consulting the reference literature or the Mass Bank, Chemical Book network database. Results: A total of 54 compounds were finally identified in this research, including the phenolic acids, flavones, terpenoids, anthraquinones, alkaloids and others. Conclusion: A method was established in this study to identify various chemical constituents of Shensong Yangxin Capsule systematically, rapidly and accurately. The identified chemical components mostly cover the main constituents of each medicinal material in the formula. Our work will lay a scientific foundation for the bioactive components screening, quality control improvement and further clinical application of this herbal formulation.
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<p><b>Background</b>Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy.</p><p><b>Methods</b>We used 2 μl (10 mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR). Therefore, it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed. Then, NRCMs were treated with 1 μl of different concentrations of SSYX (0.25, 0.5, and 1.0 μg/ml) for another 24 h. To explore the time-depend effect of SSYX on energy metabolism, 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h. Mitochondria was assessed by MitoTracker staining and confocal microscopy. mRNA and protein expression of mitochondrial biogenesis-related genes - Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), energy balance key factor - adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor - carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor - glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis.</p><p><b>Results</b>With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml), an increased mitochondrial density in AngII-induced cardiomyocytes was found compared to that of those treated with AngII only (0.25 μg/ml, 18.3300 ± 0.8895 vs. 24.4900 ± 0.9041, t = 10.240, P < 0.0001; 0.5 μg/ml, 18.3300 ± 0.8895 vs. 25.9800 ± 0.8187, t = 12.710, P < 0.0001; and 1.0 μg/ml, 18.3300 ± 0.8895 vs. 24.2900 ± 1.3120, t = 9.902, P < 0.0001; n = 5 per dosage group). SSYX also increased the mRNA and protein expression of PGC-1α (0.25 μg/ml, 0.8892 ± 0.0848 vs. 1.0970 ± 0.0994, t = 4.319, P = 0.0013; 0.5 μg/ml, 0.8892 ± 0.0848 vs. 1.2330 ± 0.0564, t = 7.150, P < 0.0001; and 1.0 μg/ml, 0.8892 ± 0.0848 vs. 1.1640 ± 0.0755, t = 5.720, P < 0.0001; n = 5 per dosage group), AMPK (0.25 μg/ml, 0.8872 ± 0.0779 vs. 1.1500 ± 0.0507, t = 7.239, P < 0.0001; 0.5 μg/ml, 0.8872 ± 0.0779 vs. 1.2280 ± 0.0623, t = 9.379, P < 0.0001; and 1.0 μg/ml, 0.8872 ± 0.0779 vs. 1.3020 ± 0.0450, t = 11.400, P < 0.0001; n = 5 per dosage group), CPT-1 (1.0 μg/ml, 0.7348 ± 0.0594 vs. 0.9880 ± 0.0851, t = 4.994, P = 0.0007, n = 5), and GLUT-4 (0.5 μg/ml, 1.5640 ± 0.0599 vs. 1.7720 ± 0.0660, t = 3.783, P = 0.0117; 1.0 μg/ml, 1.5640 ± 0.0599 vs. 2.0490 ± 0.1280, t = 8.808, P < 0.0001; n = 5 per dosage group). The effect became more obvious with the increasing concentration of SSYX. When 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h, the expression of AMPK (6 h, 14.6100 ± 0.6205 vs. 16.5200 ± 0.7450, t = 3.456, P = 0.0250; 12 h, 14.6100 ± 0.6205 vs. 18.3200 ± 0.9965, t = 6.720, P < 0.0001; 24 h, 14.6100 ± 0.6205 vs. 21.8800 ± 0.8208, t = 13.160, P < 0.0001; and 48 h, 14.6100 ± 0.6205 vs. 23.7400 ± 1.0970, t = 16.530, P < 0.0001; n = 5 per dosage group), PGC-1α (12 h, 11.4700 ± 0.7252 vs. 16.9000 ± 1.0150, t = 7.910, P < 0.0001; 24 h, 11.4700 ± 0.7252 vs. 20.8800 ± 1.2340, t = 13.710, P < 0.0001; and 48 h, 11.4700 ± 0.7252 vs. 22.0300 ± 1.4180, t = 15.390; n = 5 per dosage group), CPT-1 (24 h, 15.1600 ± 1.0960 vs. 18.5800 ± 0.9049, t = 6.048, P < 0.0001, n = 5), and GLUT-4 (6 h, 10.2100 ± 0.9485 vs. 12.9700 ± 0.8221, t = 4.763, P = 0.0012; 12 h, 10.2100 ± 0.9485 vs. 16.9100 ± 0.8481, t = 11.590, P < 0.0001; 24 h, 10.2100 ± 0.9485 vs. 19.0900 ± 0.9797, t = 15.360, P < 0.0001; and 48 h, 10.2100 ± 0.9485 vs. 14.1900 ± 0.9611, t = 6.877, P < 0.0001; n = 5 per dosage group) mRNA and protein increased gradually with the prolongation of drug action time.</p><p><b>Conclusions</b>SSYX could increase myocardial energy metabolism in AngII-induced cardiac hypertrophy. Therefore, SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.</p>
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Animals , Rats , Angiotensin II , Metabolism , Cardiomegaly , Drug Therapy , Energy Metabolism , Medicine, Chinese Traditional , Myocardium , Myocytes, CardiacABSTRACT
OBJECTIVE:To observe therapeutic efficacy and safety of metoprolol combined with Shensong yangxin capsule in the treatment of ventricular premature beat. METHODS:A total of 104 patients with ventricular premature beat during Jan. 2016-Jan. 2017 were analyzed retrospectively,and they were divided into control group(52 cases)and observation group(52 cases)according to medication plan. Control group was given Metoprolol tartrate tablet 25 mg orally,3 times a day. Observation group was given Shensong yangxin capsule 1.2 g orally,3 times a day,on the basis of control group. Both groups were treated for consecutive 28 d. Clinical efficacies of 2 groups were observed. The electrocardiogram P-R interval and Q-T interval,24 h premature beat times,heart rate,the occurrence of palpitation before and after treatment and ADR were observed. RESULTS:Total response rate of observation group(92.30%)was significantly higher than that of control group(76.92%),with statistical significance(P<0.05).Before treatment, there was no statistical significance in electrocardiogram P-R interval and Q-T interval,24 h premature beat times,heart rate or palpitation times between 2 groups(P>0.05). After treatment,electrocardiogram P-R interval and Q-T interval of 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group. 24 h premature beat times,palpitation times of 2 groups and heart rate of control group were significantly lower than before treatment;and 24 h premature beat times,palpitation times of the observation group was significantly lower than the control group,with statistical significance(P<0.05);there was no statistical significance in heart rate of observation group before and after treatment(P>0.05). There was no statistical significance in the total incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:For ventricular premature beat,metoprolol combined with Shensong yangxin capsule show significant therapeutic efficacy,can reduce the times of premature beat and improve patients'electrocardiogram without increasing the occurrence of ADR.
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OBJECTIVE:To observe therapeutic efficacy and safety of Shensong yangxin capsules combined with edaravone in the treatment of cerebrovascular disease complicated with cerebrocardiac syndrome(CCS). METHODS:A total of 128 cerebrovas-cular disease patients with CCS were randomly divided into control group (64 cases) and observation group (64 cases). Control group received routine treatment,observation group was additionally given Shensong yangxin capsule 1.6 g orally,3 times a day+Edaravone injection 30 mg added into 0.9% Sodium chloride solution 250 mL intravenously,2 times a day. Treatment courses of 2 groups lasted for 10 d. Clinical efficacies of 2 groups were observed,and MDA,SOD,catecholamine(NE,E,DA)levels,cT-nI,NIHSS scores,correlation of cTnI level with NIHSS score were also observed before and after treatment. The occurrence of ADR was recorded. RESULTS:Total response rate of nervous system and electrocardio gram in observation group were significant-ly higher than control group,with statistical significance (P<0.05). Before treatment,there was no statistical significance in MDA,SOD,NE,E,DA,cTnI levels or NIHSS scores between 2 groups(P>0.05). After treatment,MDA,NE,E,DA,cTnI levels and NIHSS scores of 2 groups were significantly lower than before,and the observation group was significantly lower than the control group;SOD of 2 groups were significantly higher than before,and the observation group was significantly higher than the antrol group,with statistical significance (P<0.05). cTnI level was positively correlated with NIHSS score (r=0.956,P=0.001). There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Based on rou-tine treatment,Shensong yangxin capsules combined with edaravone can significantly improve therapeutic efficacy of cerebrovascu-lar disease patients with CCS,and improve the levels of catecholamine,MDA and SOD without increasing the occurrence of ADR.
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OBJECTIVE:To observe therapeutic efficacy and safety of Shensong yangxin capsule combined with low-dose ami-odarone in the treatment of ventricular tachyarrhythmia. METHODS:In retrospective analysis,106 patients with ventricular tachyar-rhythmia were divided into control group and observation with 53 cases in each group according to drug use. Based on conventional treatment,control group was additionally given Amiodarone tablet (first week:0.2 g each time,3 times a day;second week:0.2 g each time,2 times a day;third week to the end of the treatment:0.2 g each time,1 times a day),orally. Observation group was given Amiodarone tablet (first week:0.2 g each time,twice a day;second week to the end of the treatment:0.2 g each time,1 times daily),orally +Shensong yangxin capsule 1.6 g,3 times a day,orally. Both groups were treated for 8 weeks. Clinical effica-cy,blood pressure,heart rate and electrocardiogram(PR period and QT period)and the cardiac cardioversion time were compared between 2 groups,and the occurrence of ADR was also recorded during treatment. RESULTS:After treatment,total response rate of observation group(94.34%)was higher than that of control group(81.13%),the incidence of ADR was lower than that of con-trol group (3.77% vs. 13.21%) and the cardiac cardioversion time was shorter than that of control group,with statistical signifi-cance(P0.05). CONCLUSIONS:Based on conventional treatment, Shensong yangxin capsule combined with low-dose amiodarone have good therapeutic efficacy with rapid response for ventricular arrhythmia,it can significantly improve the heart rate of the patients,and the effect is faster with good safety .
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Objective To study the effect of Snsong Yangxin capsule and metoprolol sustained release tablet on the curative effect and the levels of BNP and HR in the elderly coronary heart disease (CHD) arrhythmia patients. Methods It selects 108 patients with coronary heart disease and arrhythmia in elderly patients were divided into observation group (54 cases) and control group (54 cases). The control group was treated with metoprolol sustained-release tablets, and the observation group was treated with Shensong Yangxin capsule and metoprolol sustained-release tablets. The curative effect of two groups and the changes of BNP and HR levels before and after treatment were observed and compared. Results The treatment effect, times of contraction, frequency of cardiac fibrillation, frequency of defect, load, time, blood pressure and BNP of the observation group were significantly better than those of the control group (P<0.05). Conclusion For elderly patients with coronary heart disease arrhythmia, the treatment of Shensong Yangxin capsule combined with metoprolol sustained release tablets is effective. It can significantly improve the patient's heart rate, restore the blood supply to the heart, improve the blood pressure and BNP, with less adverse reactions, safe and reliable, and worthy of promotion.
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Objective To investigate the effect of Shensong Yangxin capsule on cardiac remodelling of myocardial infarction mouse model and the possible molecular mechanisms. Methods Adult male C57BL/6J mice were divided into sham operation group(n=10), model control group(n=20)and Shensong Yangxin group(n=20)according to random number table. Left anterior descending branch of coronary artery was ligated to establish myocardic infarction model in the model control group and Shensong Yangxin group. From the 2nd day after the surgery, Shensong Yangxin ( 400 mg . kg-1 ) was intragastrically administered, and the death rate of the mice was observed.Four weeks after the surgery, echocardiography was used to measure the cardiac function;myocardiac infarction area was detected by pathological staining;the expression levels of cardiac remodelling markers and extracellular matrix proteins were detected by RT-PCR. The possible molecular mechanisms were screened by Western blotting. Results As compared with the model control group, Shensong Yangxin significantly reduced the mortality after myocardial infarction in mice(P<0.05), as well as the myocardial infarct size(P<0.05).The mRNA expression levels of cardiac remodelling markers ANP, BNP, and β-MHC and the extracellular matrix proteins(collagenⅠ, collagen Ⅲ, CTGF, TGFβ) decreased significantly in the Shensong Yangxin group as compared with the model control group. Western blotting showed that Shensong Yangxin significantly decreased activation of smad3, and reduced expression level of smad4. Conclusion Shensong Yangxin attenuates cardiac remodelling after myocardial infarction and the mechanism may be related with blockage of smad signaling pathway.
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Objective: To develop a ultra performance liquid chromatography (UPLC) method for the quality evaluation of Shensong Yangxin Capsule (SYC). Methods: The Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used. Acetonitrile and water containing 0.1% phosphoric acid were used as mobile phases of UPLC with gradient elution. The detection wavelengths were set at 203 (ginsenoside Rb1), 286 (salvianolic acid B), 230 (paeoniflorin), 221 (schisantherin A), 280 (sodium danshensu), 327 (chlorognenic acid), 335 (spinosin), and 345 nm (berberine hydrochloride), respectively. The flow rate was set at 0.4 mL/min and column temperature was 35 °C. Results: The contents of paeoniflorin, salvianolic acid B, schisantherin A, sodium danshensu, chlorognenic acid, spinosin, berberine hydrochloride, and ginsenoside Rb1 were determined from 10 batches of SYC. Conclusion: The method of the quality evaluation of SYC has acceptable precision, reproducibility, and stability, which could be used as a new method for the quality control of SYC. © 2013 Tianjin Press of Chinese Herbal Medicines.
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Objective To observe the effect of different pore diameter membranes on technologies of water extract from Shensong Yangxin Capsule and optimize the parameters. Methods Three different membranes were tested to observe the changes in membrane flux and the retention of effective components. Results The membrane with 100 nm diameter had the greater membrane flux, the transfer rates of paeoniflorin was the highest. The optimum conditions were that the operation differential pressure was 0.15-0.22 MPa, the operation temperature was 20°C. Conclusion A good result can be obtained by adopting the technology of ceramic membranes filtration to purify Shensong Yangxin Capsule, which provides the foundation for the application of ceramic membranes micro-filtration in the purification of water extract of other Chinese materia medica.
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OBJECTIVE:To observe the efficacy and safety of adjuvant Shensong Yangxin Capsule(SYC)in patients with stable angina(SA)receiving conventional therapy.METHODS:Fifty-eight chronic stable angina(CSA)patients were randomly assigned to 2 groups:the SYC group(n=28)treated with SYC plus conventional therapy while the control group(n=28)with conventional therapy alone.The patients were allowed to take nitroglycerine if number of the angina attacks ≥ 2 per day.The course of treatment fro both groups was 12 weeks.RESULTS:The total ischemic time during 24 hours,the ST segment decreasing amplitude and the frequency of angina pectoris attacks in two groups were all improved significantly after treatment(P