The Different Therapeutic Effects of Traditional Chinese Medicine Shensong Yangxin Capsule and Salubrinal in High-intensity Exercise-induced Heart Failure in Rats with Acute Myocardial Infarction.

BACKGROUND: Currently, endoplasmic reticulum stress is studied utilizing a dephosphorylation inhibitor (Sal). The traditional Chinese patent medicine and simple formulation Shensong Yangxin Capsule is a commonly used medication for the treatment of arrhythmia. However, the efficacy and underlying mechanism of the capsule in treating post-ischemic heart failure in myocardial tissue have not yet been investigated. OBJECTIVE: The therapeutic effects and the underlying mechanism of the Shensong Yangxin Capsule (SSYX) and the dephosphorylation inhibitor Salubrinal (Sal) on heart failure (HF) induced by high-intensity exercise in rats with acute myocardial infarction (AMI) were investigated. METHODS: Male infants of 8 weeks Spragge-Dawley (SD) rats were randomly assigned to one of four groups: sham surgery group, AMI+placebo group, AMI+Shensong Yangxin Capsule group (AMI+SSYX), and AMI+Sal administration group. Rats' myocardial infarction was induced by left coronary artery ligation. Rats were subjected to a 3-week high-intensity exercise program to simulate heart failure after 7 days of postoperative rest. After the fourth postoperative week, echocardiography was applied to determine the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular systolic volume (LVESV) in each group. HE and TUNEL labeling were employed to examine the morphology of cardiac cells and measure the percentage of apoptosis in each group; Western blotting was applied to detect the cardiomyocyte apoptosis-related proteins p-JNK, p-P38, and NOX2, while ELISA was used to detect glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum. RESULTS: Following a 4-week drug intervention:(1)LVFS and LVEF in the AMI+placebo group were statistically significantly reduced, while LVESV were significantly higher, compared to those in the sham surgery group (P<0.05); The AMI+SSYX group performed statistically significantly better than the AMI+placebo group(P<0.05). (2) The myocardial cells in the AMI+placebo group exhibited significant swelling and inflammatory cell infiltration; the myocardial cells in the AMI+SSYX group and AMI+Sal group displayed mild swelling and minimal inflammatory cell infiltration; the AMI+SSYX group's myocardial cell morphology was superior to that of the AMI+Sal group; (3) The apoptosis rate of the AMI+placebo group was around 95%, greater than that of the sham surgery group (2.55%). The apoptosis rate of the AMI+SSYX group is approximately 21%, while the apoptosis rate of the AMI+Sal group is about 43%. (4) In the AMI+placebo group, p-JNK, p-P38, and NOX2 protein expression dramatically increased compared to the sham surgery group. The expression of p-P38, NOX2, and p-JNK/t-JNK was considerably reduced in the AMI+Shensong group and AMI+Sal group, compared to the AMI+placebo group. (P<0.01)The AMI+SSYX group's result is superior to that of the AMI+Sal group. (5) Compared to the sham surgery group, the serum levels of SOD and GSH were significantly lower, and MDA was significantly higher in the AMI+placebo group. Compared to the AMI+placebo group, the serum levels of SOD and GSH were significantly higher, and MDA was significantly lower in the AMI+SSYX group and the AMI+Sal group. (P<0.05) Conclusion: In rats with acute myocardial infarction in high-intensity exercise-induced heart failure, Shensong Yangxin Capsule dramatically reduces myocardial cell death and cardiac dysfunction. SSYX has a shorter course of treatment and a better therapeutic effect than Sal.

Clinical Efficacy and Safety of Shensong Yangxin Capsule-Amiodarone Combination on Heart Failure Complicated by Ventricular Arrhythmia: A Meta-Analysis of Randomized Controlled Trials.

Background: Shensong Yangxin capsule (SSYX) is a well-known traditional Chinese patent medicine for treating arrhythmia. Recently, a flurry of randomized controlled trials (RCTs) of SSYX combined with amiodarone (SSYX-amiodarone) was reported in the treatment of heart failure (HF) complicated by ventricular arrhythmia (VA) in China. However, these RCTs have not been systematically evaluated. Therefore, this study aimed to evaluate the efficacy and safety of SSYX-amiodarone in the treatment of heart failure complicated by ventricular arrhythmia (HF-VA). Methods: Seven electronic literature databases (the Cochrane Library, PubMed, EMBASE, China Biomedical database web, China National Knowledge Infrastructure Databases, Chinese Scientific Journal database and Wanfang database) were searched from their inceptions to June 1, 2020 to identify RCTs of SSYX-amiodarone in the treatment of HF-VA. The primary outcomes included the total effective rate and adverse events (ADRs). The secondary outcomes included the frequency of ventricular premature complexes, left ventricular ejection fraction, N terminal pro Btype natriuretic peptide (NT-proBNP), and QT dispersion (QTd). The quality of the included RCTs was assessed using the Cochrane risk-of-bias tool. All data was analyzed using RevMan 5.3 software. The registration number of this protocol is PROSPERO CRD42020196689. Results: There are Eighteen trials involving 1,697 patients were included in this study. Meta-analysis showed that SSYX-amiodarone group was superior to the amiodarone group in improving the total effective rate [RR = 1.21; 95%CI (1.16, 1.27); p < 0.01], meanwhile reducing the ADRs [RR = 0.65; 95%CI (0.45, 0.95); p = 0.03], VPCs [MD = 170.96; 95%CI (159.88, 182.04); p < 0.01] and QTd [MD = 8.39; 95%CI (6.91, 9.87); p < 0.01]. No significant difference of enhancing LVEF [MD = 4.32; 95%CI (-0.56, 9.20); p = 0.08] and reducing NT-proBNP [SMD = 0.17; 95%CI (-0.81, 1.14); p = 0.73] was observed between SSYX-amiodarone and amiodarone group. Conclusions: Despite the apparent positive findings reported, the evidence provided by this meta-analysis was still insufficient to support the routine use of SSYX-amiodarone for HF-VA due to the poor methodological quality of included studies. The overall effect should to be verified in further through more well-design clinical studies with reasonable sample and good methodological quality.

Chinese Medicine Shensong Yangxin Capsule () Ameliorates Myocardial Microcirculation Dysfunction in Rabbits with Chronic Myocardial Infarction.

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.

Chinese Medicine Shensong Yangxin Capsule () Ameliorates Myocardial Microcirculation Dysfunction in Rabbits with Chronic Myocardial Infarction / 中国结合医学杂志

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.

Study on chemical constituents of Shensong Yangxin Capsule based on UHPLC-Q-Orbitrap HRMS / 中草药

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.

Shensong Yangxin capsule reduces atrial fibrillation susceptibility by inhibiting atrial fibrosis in rats with post-myocardial infarction heart failure.

PURPOSE: Shensong Yangxin (SSYX) capsule is a traditional Chinese medicine that has been used widely to treat cardiac arrhythmia. This study aimed to assess whether SSYX prevents atrial fibrillation (AF) after chronic myocardial infarction (MI)-induced heart failure and to determine the underlying mechanisms. MATERIALS AND METHODS: The study included 45 male Sprague Dawley rats. The rats underwent MI induction or sham surgery. One week after MI induction surgery, we performed serial echocardiography and administered SSYX capsule to some rats that experienced MI. After 4 weeks of treatment, AF inducibility was assessed with transesophageal programmed electrical stimulation technology. Additionally, multielectrode array assessment, histological analysis, and Western blot analysis were performed. RESULTS: AF inducibility was significantly lower in SSYX rats than in MI rats (33.3% vs 73.3%, P<0.05). Additionally, conduction velocities in the left atrium were greater in SSYX rats than in MI rats. Moreover, SSYX decreased left atrial fibrosis, downregulated TGF-ß1, MMP-9, TIMP-I, and type I and III collagen expressions, and inhibited the differentiation of cardiac fibroblasts to myofibroblasts. CONCLUSION: SSYX reduces AF inducibility after MI by improving left atrial conduction function via the inhibition of left atrial fibrosis. It prevents the development of an MI-induced vulnerable substrate for AF.

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-Induced Cardiac Hypertrophy.

BACKGROUND: 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. METHODS: We used 2 µl (10-6 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical Observation of Metoprolol Combined with Shensong Yangxin Capsule in the Treatment of Ventricular Premature Beat / 中国药房

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.

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-Induced Cardiac Hypertrophy / 中华医学杂志(英文版)

<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>

Clinical Observation of Shensong Yangxin Capsules Combined with Edaravone in the Treatment of Cere-brovascular Disease Complicated with Cerebrocardiac Syndrome / 中国药房

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.

Effect of ginseng Shensong Yangxin capsule and metoprolol sustained release tablet on the curative effect and the levels of BNP and HR in elderly patients with coronary heart disease with arrhythmia / 中国生化药物杂志

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.

Analysis of Therapeutic Efficacy of Shensong Yangxin Capsule Combined with Low-dose Amiodarone in the Treatment of Ventricular Tachyarrhythmia / 中国药房

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 .

Effect of Shensong Yangxin Capsule on Cardiac Remodelling of Myocardial Infarction Mouse Model / 医药导报

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.

Spiroalkaloids from Shensong Yangxin capsule.

Four spiroalkaloids, including a new compound shensongine A (1), were isolated from the anti-arrhythmic TCM formula Shensong Yangxin capsule. Their structures were determined on the basis of spectroscopic analysis. Compounds 1 and 3 displayed cardiovascular activities by shortened APD in rat myocardial cells. These compounds were possibly generated from precursors in different composed herbal medicines during the processing of the TCM formula.

Shensong Yangxin Capsule prevents diabetic myocardial fibrosis by inhibiting TGF-ß1/Smad signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Shensong Yangxin Capsule (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the effect of SSYX on interstitial fibrosis in diabetic cardiomyopathy is unknown. The objective of this study was to investigate the effects of SSYX on myocardial fibrosis in diabetic rats. MATERIALS AND METHODS: The antifibrotic effect of SSYX was investigated in streptozocin (STZ)-induced diabetic rats with high fat-diet (HFD). Fasting blood glucose, heart weight/body weight (HW/BW) ratio, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured. Echocardiography and histology examination were carried out to evaluate heart function. Expressions of Smad7, TGF-ß1, collagen I (col-1), collagen III (col-3), MMP-2, MMP-9 and α-SMA mRNA in heart tissues were measured by real time polymerase chain reaction (PCR). TGF-ß1, Smad2/3, p-Smad2/3 and Smad7 protein levels were measured by western blot analysis. Proliferation of cardiac fibroblast was detected via immunofluorescence. RESULTS: SSYX markedly decreased HW/BW ratio and improved the impaired cardiac function of type-2 diabetes mellitus (T2DM) rats. Transmission electron microscopy (TEM), haematoxylin and eosin (HE) and Masson staining results showed that SSYX attenuated cardiac fibrosis and collagen deposition in T2DM rats. Moreover, mRNA levels of TGF-ß1, col-1, col-3, MMP-2, MMP-9 and α-SMA were downregulated, whereas Smad7 expression was upregulated after treatment with SSYX in rats with cardiac fibrosis. Furthermore, SSYX decreased protein levels of TGF-ß1 and p-Smad2/3, and increased Smad7 expression. CONCLUSION: TGF-ß1/Smad signaling is involved in the cardiac fibrosis in diabetic cardiomyopathy and SSYX inhibits fibrosis and improves cardiac function via suppressing this pathway. Therefore, SSYX might be considered as an alternative therapeutic remedy for diabetic cardiomyopathy.

Studies on excretion kinetics of ten constituents in rat urine after oral administration of Shensong Yangxin Capsule by UPLC-MS/MS.

A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of 10 major active constituents in rat urine after oral administration of Shensong Yangxin Capsule (SSYX) using diazepam as an internal standard (IS). The urine samples were pretreated and extracted by solid-phase extraction prior to UPLC. Chromatographic separation was achieved on a Waters C18 (2.1 × 50 mm, 1.7 µm) column using a gradient elution program with 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.4 mL/min. Detection and quantitation were accomplished by a hybrid quadrupole mass spectrometer using electrospray ionization source and multiple reaction monitoring in the positive ionization mode. The mass transition ion-pairs (m/z) for quantitation were all optimized and the total run time was 4.50 min. The specificity, linearity, accuracy, precision, recovery, matrix effect and stabilities were all validated for the analytes in urine samples. The validation results indicated that this method was simple, rapid, specific and reliable. The proposed method was successfully applied to investigate the urinary excretion kinetics of 10 compounds in rat after oral administration of SSYX.

Simultaneous determination of eight bioactive constituents in Shensong Yangxin capsule by UPLC / 中草药·英文版

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.

Application of ceramic filter membrane in purification technology of water extract from Shensong Yangxin Capsule / 中草药

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.

Curative Efficacy of Shensong Yangxin Capsule for Stable Angina / 中国药房

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