Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains

Shengmai Yin(SMY)is a Chinese herbal decoction that effectively alleviates the side effects of radiotherapy in various cancers and helps achieve radiotherapy’s clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma(NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells(CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genomewide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the differential gene Tenascin-C(TNC)was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3 a may be the key protein in DNA methylation of TNC.

Combination of Shengmai San and Radix puerariae ameliorates depression-like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression

Background:Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression.Diabetic individuals are more vulnerable to experience depression compared to the normal population.Thus,novel treatment approaches are required to reduce depressive symptoms among diabetic individuals.Traditional Chinese medicines(TCMs)such as Shengmai San(SMS)and Radix puerariae(R)are usually widely used to treat ailments such as neurological com-plications since ancient time.Methods:In this study,SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats.The antidepressant po-tential of the prepared combination was evaluated behaviorally using open field test,novelty-induced hypophagia,and forced swim test in diabetic rats with biochemical and protein expression(PI3K,BDNF[brain-derived neurotrophic factor],and SYN[pr-esynaptic vesicle protein])analysis.Results:Diabetic rats(streptozotocin,45 mg/kg)showed elevated fasting blood glu-cose(FBG)>12 mM with depressive symptoms throughout the study.Treatment with R-SMS(0.5,1.5,and 4.5 g/kg)significantly reverted depressive symptoms in diabetic rats as evinced by significantly(p<0.05)reduced immobility time with an increased tendency to eat food in a novel environment.Treatment with R-SMS also significantly increased the protein expression of PI3K,BDNF,and SYN protein,which play a crucial role in depression.Conclusion:This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats;thus,this formulation might be studied further to develop as an antidepressant.

Optimal scheme of Shengmai Injection in the treatment of angina pectoris of coronary heart disease based on Louvain algorithm: A real world study

Objective:To explore the optimal scheme of Shengmai Injection combined with other drugs for clinical doctors.Methods:Based on the large-scale data warehouse established by the institute of Clinical Basic Medicine,Chinese Academy of Traditional Chinese Medicine,the hospital information system of 22 large-scale tertiary hospitals in China was collected and 1751 patients with angina pectoris who were treated with Shengmai Injection were selected.Louvain algorithm and complex network analysis are used to build the model to summarize the rule of Shengmai Injection in the treatment of angina pectoris of coronary heart disease.Results:On the basis of Shengmai Injection,according to the symptom treatment of angina pectoris of coronary heart disease,nitrates or Suxiao Jiuxin Pill was used to dilate coronary artery;for the treatment of risk factors of angina pectoris,a combination of"insulin+acarbose+bisoprolol+nifedipine+captopril+estazolam"was used to control blood glucose and blood pressure;"Ganmao Qingre Granule+levofloxacin"to treat upper respiratory tract infection and other medication regimens were used as well.For the complications of angina pectoris of coronary heart disease,"furosemide+spironolactone+potassium chloride+magnesium sulfate"was used to reduce edema and“isosorbide nitrate+metoprolol+Shenmai injection+Wenxin Granule"was used to improve symptom of heart failure of qi and yin deficiency type.Conclusion:The therapeutic regimen of Shengmai Injection combined with traditional chinese medicine and western medicine is basically consistent with the current guidelines,but more clinical studies are still needed to explore more effective combination therapy.

Network analysis and molecular docking of the mechanism of Shengmai decoction in treating patients with severe novel coronavirus pneumonia

Background:Studies have shown that,Shengmai injection(Shengmai decoction)which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.However,the mechanism of its intervention in severe stage of COVID-19 at molecular level is still unclear.Therefore,it is necessary to further explore the mechanism of Shengmai decoction in the treatment of patients with severe COVID-19 based on network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology,BATMAN,UniProt databases and the published literatures which contain the reported compounds that have therapeutic effects on COVID-19 were used to screen out the active ingredients and targets of Shengmai decoction,and the“drug-active compound-target”network was constructed.The GeneCards database was used to screen out the targets of COVID-19.The protein-protein interaction network map was constructed by mapping two genes,and the network of active ingredients,targets and disease was constructed using Cytoscape software.Thereafter,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the key targets were performed using the Metascape Site Maintenance website and David databases.The Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the mapping targets were analyzed.Results:The active component-target network contained 73 main compounds and 457 targets.The first five main active components(hydroquinone,guanosine,ophiopogon C,ophiopogon B,ophiopogon D)were obtained by topological analysis of 33 common targets.Using the Matthews correlation coefficient algorithm,the key targets included albumin,tumor necrosis factor,and cyclic adenosine response element binding.Compounds in Shengmai decoction were found to have good binding effect and strong interaction with caspase-8,caspase-3,apoptosis regulator Bcl-2,tumor necrosis factor,C-C motif chemokine 3,to inhibit the inflammatory response and improve lung injury.Additionally,31 biological processes were obtained by Gene Ontology enrichment,mainly related to lipopolysaccharide response and cytokine-mediated signal pathways,and 71 biological processes were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment,mainly related to pulmonary tuberculosis,hepatitis B,and mitogen-activated protein kinase signal pathways.Conclusion:Shengmai decoction has multicomponent,multitarget and multichannel characteristics,which can provide an important theoretical basis to treat patients with severe COVID-19.

Observation on Therapeutic Effects of Shengmai Powder (生脉散)in Treating Acute Viral Myocarditis

Objective: To evaluate the clinical efficacy of Shengmai Powder (SMP, 生脉散) in treating a-cute viral myocarditis objectively. Methods: One hundred and twenty-four patients with acute viral myocarditis were randomized into the treated group (SMG, n = 64) and the control group(CG, n = 60 ). Such myo-cardial nutrient medicine as ATP, CoA , Vit-C, were given to both groups. And to the treated group, 40 ml of Shengmai Injection per day was given intravenously for 2 weeks, which was followed by oral intake of Shengmai granule, one package three times daily for another 2 weeks in total. The same anti-arrhythmia agents were applied to both groups, and no fructose-1, 6-diphosphate (FDP) for either. Semi-quantitative scoring method was adopted to observe such symptoms as chest stuffiness, palpitation and chest pain before treatment and four weeks after treatment. Meanwhile, EGG, dynamic ECG by Holter monitor, left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), serum neutralizing antibody of virus Coxsackie B, cardiac troponin I (cTnl) and cardiac troponin T (cTnT) were examined. Results: (1) Compared with the control group, more significant improvement was got in SMG in respects of chest stuffiness, palpitation, chest pain and arrhythmia (P<0.05 or P<0.01). (2) Negative converting rates of cTnl ,cTnT in the two groups were 59.46% vs35.48%, 68.75% vs42.31% respectively ( P<0. 05). (3) LVEDD before and after treatment in SMG was 52. 44 ± 3. 40 mm and 48. 81 ± 2. 23mm respectively, while that in the control group was 52. 31 ± 3. 74 mm and 49. 92 ± 2. 67mm respectively; LVEF before and after treatment in SMG was 60.67 ± 4. 62 % and 65. 02 ± 4. 16 % respectively, while that in the control group was 60.91 ± 4. 26 % and 63. 67 ± 3.17 % . There was obvious improvement in the two parameters in both groups, but the improvement in SMG was superior to that in the control group ( P<0. 05). Conclusion: SMP shows a good effect in improving clinical symptoms and signs, heart function, abnormal ECG and inflammatory injury indexes in patients with acute viral myocarditis.

Shengmai Suppressed Vascular Tension in Umbilical Arteries and Veins of Human and Sheep

Objective—The umbilical cord is a critical pathway between mothers and fetuses, and regulations of umbilical vessel tension are important for fetal growth. Shengmai is an herbal medicine being used in treatments of cardiovascular diseases. However, effects of Shengmai on human blood vessels and related pharmacological mechanisms are unclear. Methods—This study investigated the effects of related mechanisms of Shengmai and its key compounds on human and sheep umbilical arteries and veins using organ bath systems. Key Findings—Shengmai significantly suppressed phenylephrine-stimulated vasoconstriction in umbilical arteries and veins. NG-Nitro-L-arginine Methyl Estercould not change the Shengmai-suppressed vasoconstriction in human and sheep umbilical vessels. Among four key compounds of Shengmai, Ginsenoside Re, Ginsenoside Rb1, Ginsenoside Rg1, and Schisandrin, only Ginsenoside Re showed the significant effect similar to Shengmai’s in the umbilical vessels. In Ca2+-free solution, Ginsenoside Re did not affect vasoconstriction. In addition, caffeine- or phenylephrine-stimulated vasoconstriction were not changed by Ginsenoside Re. Either charybdotoxin or glibenclamide could inhibit Ginsenoside Re-caused inhibition of the stimulated vasoconstriction in both human and sheep umbilical vessels, where 4-aminopyridine did not show the similar inhibitory effect. Conclusion—The results provide new information on Shengmai’s effects and underlying mechanisms in umbilical vessels. Importantly, the information gained offers interesting potential for developing new drugs acting on umbilical cords for fetal medicine.

Effectiveness of Shengmai Injection on angina pectoris based on real-world propensity score method

Objective:Shengmai injection is a commonly used traditional Chinese medicine for the treatment of angina pectoris.However,there is still a lack of high-quality clinical research evidence for the treatment effect of Shengmai injection for angina pectoris.Real-world studies based on large samples can provide Shengmai injection.Researches on the treatment of angina pectoris with Shengmai injection provide important evidence.Methods:This article is based on the information collected by the hospital information system(HIS)database of 22 tertiary A general hospitals for all patients who used Shengmai injection and those who did not use Shengmai injection.The propensity scoring method was used to evaluate the possible existence of the research data.The confounding factors are controlled.Through the general Logistic regression analysis method,the propensity score weighted Logistic regression analysis method and the propensity score weighted Logistic regression analysis method with covariates,the therapeutic effect of Shengmai injection on angina pectoris was explored.Results:Three kinds of logistic regression analysis showed that there were statistical differences in the treatment effect of Shengmai injection on angina pectoris in the group without Shengmai injection.Propensity score weighted logistic regression analysis with covariates balanced the effect of multiple confounding factors.Using real-world data to construct a retrospective cohort study confirmed the clinical effectiveness of Shengmai injection in the treatment of angina pectoris,and at the same time confirmed the wide application of Shengmai injection in angina pectoris complicated with multiple organ failure.Conclusion:Shengmai injection is effective in the treatment of angina pectoris.The weighted method of propensity score removes confounding factors,which improves the reliability of real-world research results.

Effects of Dengzhan Shengmai Capsule combined with antiplatelet drug and statin therapy on platelet function, inflammatory response and lipid metabolism in patients with unstable angina pectoris

Objective: To study the effects of Dengzhan Shengmai Capsule combined with antiplatelet drug and statin therapy on platelet function, inflammatory response and lipid metabolism in patients with unstable angina pectoris. Methods: A total of 96 patients who were diagnosed with unstable angina pectoris for the first time in Beijing Shunyi District Hospital of Traditional Chinese Medicine between February 2015 and January 2018 were chosen and randomly divided into two groups, the observation group received Dengzhan Shengmai Capsule combined with antiplatelet drug and statin therapy, and the control group only accepted antiplatelet drug and statin therapy. Platelet function parameters, inflammatory response parameters and lipid metabolism parameters were determined before treatment and after 2 months of treatment. Results: Compared with those of same group before treatment, PAF, P-selectin, PDGF, E-selectin, Gal-3, TNF-α, IFN-γ, LDL-C, PCSK9, Chemerin and Visfatin contents in serum as well as C3aR and C5aR contents in peripheral blood platelets of both groups of patients were decreasing whereas sFGL2, TGF-β1, APN and Vaspin contents in serum were increasing after treatment, and PAF, P-selectin, PDGF, E-selectin, Gal-3, TNF-α, IFN-γ, LDL-C, PCSK9, Chemerin and Visfatin contents in serum as well as C3aR and C5aR contents in peripheral blood platelets of observation group after treatment were lower than those of control group whereas sFGL2, TGF-β1, APN and Vaspin contents in serum were higher than those of control group. Conclusion: Dengzhan Shengmai Capsule combined with antiplatelet drug and statin therapy for unstable angina pectoris can more effectively inhibit the platelet aggregation and improve the inflammatory response and lipid metabolism.

Effects of Supplemented Shengmai San (SMS) on Blood Biochemistry and HSP72 Expression in Peripheral Blood of Flying-saucer Athletes before and after High Temperature Training

Objective:The purpose of this paper is to study the effects of supplemented Shengmai San on the expression of heat shock protein 72(HSP72)and blood biochemistry in peripheral blood of flying-saucer athletes before and after high temperature training,so as to provide experimental basis for enhancing thermal endurance and preventing heat disease of flying-saucer athletes with anti-heat disease drugs.Methods:24 flying-saucer athletes from Zhejiang province were selected and divided into two groups,including control group and traditional Chinese medicine group with 12 people in each group.Among them,those who did not drink supplemented Shengmai San were in the control group,while those who drank it were in the traditional Chinese medicine group.During summer training,high temperature training task was carried out for 2 weeks.Flying-saucer athletes in traditional Chinese medicine group were given supplemented Shengmai San before training every morning and afternoon.Peripheral venous blood of each group was extracted before experiment and 2 weeks later and lymphocyte HSP72 content,blood routine and biochemical indexes were determined respectively.Results:Before the experiment,there were no abnormal phenomenon blood routine,biochemical test value and HSP72 expression in the control group and the traditional Chinese medicine group.After comparison,there was no significant difference(P>0.05).After the high temperature training,the expression of HSP72 in the Chinese medicine group was significantly higher than that before the training and control group(P<0.05).There were significant differences in white blood cell count before and after the experiment(P<0.05).Conclusion:Taking supplemented Shengmai San can significantly increase expression of HSP72 in up-regulation of flying saucer athletes after thermal stimulation,thus enhancing thermal tolerance and preventing thermal diseases.

Shenxian Shengmai Oral Liquid for treatment of slow arrhythmia： a randomized controlled trial

Background： Slow arrhythmia, a common clinical condition, has a higher incidence in the elderly population. Shenxian Shengmai Oral Liquid has been shown to improve the symptoms of patients with slow arrhythmia in many clinical studies and systematic reviews. Sixty participants with slow arrhythmia will be randomized to treatment group （Shenxian Shengmai Oral Liquid） and control group （Shenxian Shengmai Oral Liquid Placebo） in a 2：1 ratio. This clinical trial is a pilot study to compare the effects of Shenxian Shengmai Oral Liquid and the control groups; to analyze the effect of Shenxian Shengmai Oral Liquid for slow arrhythmia.

Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Effect of Shengmai Injection(生脉注射液) on Cardiac Function and Inflammatory Reaction in Patients with Acute Coronary Syndrome

Objective： To confirm the effect of Shengmai Injection （生脉注射液, SMI） in improving cardiac function in patients with acute coronary syndrome （ACS） and to explore its influence on inflammatory reaction in patients. Methods： Ninety ACS patients were randomized into two groups, the control group treated with conventional therapy and the SMI group treated with SMI. The patients＇ cardiac function was noted and the content of high sensitive C-reactive protein （hs-CRP） in venous blood was measured before treatment and 1 week and 3 weeks after treatment, so as to observe and compare their changes between the two groups. Results： The cardiac output, stroke volume and ejection fraction in the SMI group after 3 weeks of treatment were all higher than those in the control group （P〈0.05）. The serum content of hs-CRP was reduced in both groups （P〈0.05）, but the reduction in the SMI group was more significant than that in the control group （P〈0.05）. Conclusion： SMI could improve the cardiac function and further inhibit the inflammatory reaction in patients with ACS.

Effect of Shengmai Injection (生脉注射液) on Vascular Endothelial and Heart Functions in Patients with Coronary Heart Disease Complicated with Diabetes Mellitus

Objective： To study the effect of Shengmai injection （生脉注射液, SMI） on vascular endothelial and heart functions in coronary heart disease patients complicated with diabetes mellitus （CHD-DM）. Methods： One hundred and twenty patients with CHD-DM, their diagnosis confirmed by coronary arteriography, were equally randomized into a control group treated with conventional treatment and a treated group treated with conventional treatment plus SMI. The changes in blood levels of nitric oxide （NO）, endothelin-1 （ET-1） and angiotensin Ⅱ （Ang Ⅱ）, as well as endothelium-dependent vascular dilating function and heart function in the patients were observed before treatment and after the 3-week treatment. Results： After being treated with SMI for 3 weeks, in the treated group, blood level of NO was raised significantly from 69.8±33.1 μmol/L to 120.1±50.8μmol/L, and ET-1 was lowered from 70.1±32.1 ng/L to 46.2±21.3 ng/L, respectively （P〈0.01）; that of Ang Ⅱ was lowered from 81.3±24.3 ng/L to 50.2±27.3 ng/L （P〈0.01）; brachial arterial post-congestion blood flow increasing rate was raised from 389.4±26.3% to 459.3±27.8% （P〈0.01）; and the improvement in heart function as seen through the ejection fraction （EF） was increased from 44±5% to 68±6% （P〈0.01）, all the changes being more significant than those in the control group （all P〈0.01）. Conclusion： SMI can improve not only the endothelial function in CHD-DM patients, but also heart contraction significantly.

Study on the Protective Effect of the Mixture of Shengmai Powder and Danshen Decoction(生脉散丹参饮合剂)on the Myocardium of Diabetic Cardiomyopathy in the Rat Model

Objective：To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction（生脉散丹参饮合剂,abbreviated as the Mixture） in the rat model with type 2 diabetic cardiomyopathy （DCM）.Methods：Forty-two SD rats with DCM model,established by the combination of insulin resistance by a high-fat diet with the damage of pancreatic islet p cells by intraperitoneal injection of high dose streptozotocin （50 mg/kg） once,were evaluated in the damage of the myocardium by electrocardiogram at the end of 12 weeks of grouping and intervention administration;the extent of damage in the myocardial subcellular structure was observed by electron microscopy;the content of myocardial collagen in the left cardiac ventricle was quantified by Masson staining test;the myocardial cell apoptosis was determined by TUNEL;the changes in the mRNA expression levels of thrombospodin-1（TSP-1） and tribbles homolog 3（TRB-3） by real-time quantitative PCR,the expression levels of myocardial TSP-1,tumor growth factorβ1（TGF-β1）,TRB-3,and chymase were detected by immunohistochemistry,and the changes in the expression levels of myocardial TSP-1,active-TGF-β1 （A-TGF-β1） and latent-TGF-β1（L-TGF-β1） protein were tested by Western blotting.Results：Compared with the control group,the myocardial tissue was less damaged,and the extent of damage in the myocardial subcellular structure was less;the collagen fiber content and the cell apoptosis were reduced;the expression levels of TSP-1 mRNA and TRB-3 mRNA,the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and chymase,as well as the average expression levels of the myocardial TSP-1,A-TGFβ1,and L-TGF-β1 protein were decreased in the Mixture group.Conclusion：The Mixture of Shengmai Powder and Danshen Decoction could inhibit the process of myocardial fibrosis in the rat myocardium of DCM through multiple pathways and significantly delay the genesis and progress of DCM in hyperglycemic rats.

Anti-fibrotic Effects and Mechanism of Shengmai Injection(生脉注射液)on Human Hepatic Stellate Cells LX-2

Objective: To investigate the effects of Shengmai Injection(生脉注射液, SMI) on the proliferation, apoptosis and N-myc downstream-regulated gene 2(NDRG2, a tumour suppressor gene) expression in varying densities of human hepatic stellate cells LX-2. Methods: LX-2 cells were cultured in vitro. Then, cells were plated in 96-well plates at an approximate density of 2.5×10~4 cells/mL and cultured for 48, 72, 96 or 120 h followed by the application of different concentrations of SMI(0.6, 1.2, 2.4, 4.8 or 6 μL/mL). Cell proliferation was measured after an additional 24 or 48 h using the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. The effects of SMI on different cell growth states(cultured for 48, 72, 96, or 120 h) were observed by light microscopy at 24 h after treatment. When the cells reached 80% confluence, apoptosis was detected by flow cytometry after 24 h. Lastly, LX-2 cells were treated with different concentrations of SMI and extracted with protein lysis buffer. The levels of NDRG2 were measured by Western blot. Results: When the LX-2 cells grew for 48, 72, 96 and 120 h, 4.8 and 6 μL/m L of SMI significantly inhibited cell proliferation at 24 and 48 h after treatment(P<0.05). And 2.4 μL/mL of SMI also inhibited cell proliferation at 24 h after treatment when cell growth for 48 h(P<0.05) and at 48 h after treatment when cell growth for 72, 96 and 120 h(P<0.05). The NDRG2 expression level in the LX-2 cell was significantly increased when treated with SMI at concentrations of 1.2, 2.4, 4.8 or 6 μL/mL(P<0.05). Conclusions: The inhibitory effects of SMI on the proliferation of LX-2 cells were related to not only concentration dependent but also cell density. In addition, SMI(2.4, 4.8 and 6 μL/mL) could accelerate apoptosis in LX-2 cells, and the mechanism might be associated with NDRG2 over-expression.

Protection of Shengmai Recipe on Improving Cardiac Function and Attenuating Kidney Injury in Pressure Overload Rats

Objective Shengmai Recipe （SMR） is a Chinese patent medicine used for the treatment of chronic heart disease. In order to further assess the renal-protective effect against ischemia lesion of SMR, the cardioprotective effect of SMR on pressure overload-induced left ventricular （LV） systolic dysfunction and the potential mechanism on alleviating myocardial damage, myocardial fibrosis, and renal ischemia lesion in chronic heart failure （CHF） rats were investigated. Methods Rats with partially ligated abdominal aorta were randomly divided into model, Sham, and SMR groups. One week after recovery from surgery, animals were preventively ig administered with SMR at the dose of 810 mg/kg once daily for 8 weeks. Cardiac function and structure, endogenous biomarkers （CK-MB and LDH）, myocardial fibrosis, and organ pathological change were estimated by echocardiography, immunodepression and velocity method, hematoxylin- eosin staining, and masson＇s trichrome staining, respectively. Results The administration of SMR significantly decreased serum CK-MB and LDH levels and reduced myocardial fibrosis. Interestingly, SMR not only improved cardiac function but also ameliorated kidney injury induced by ischemia in CHF rats. Conclusion SMR could enhance the LV contractile function, reduce myocardial necrosis, and reverse LV remodeling in CHF rats, and most importantly, SMR could be used to treat the renal ischemia injury in pressure overload rats.

Protective Effect of Shengmai Injection on Rats with Contrast Medium-Associated Acute Renal Failure

Objective: Radiographic contrast media can induce renal failure and it may serve as an experimental model of acute renal failure (ARF). The study was aimed to determine the protective effect of Shengmai Injection (SMI) on contrast medium-associated ARF in Sprague-Dawley (SD) rats. Methods: Twenty healthy SD rats of both sex were randomly divided into two groups, Group A (control group) treated with glycerin + 0.9 % saline + meglucamine diatrizoate, and group B (preventive group) with glycerin + SMI + meglucamine diatrizoate. Results: In Group B, the levels of blood urea nitrogen, serum creatinine, renal phospholipase A2 (PLA2) and calcium were all significantly lower than those in Group A, P < 0. 01. The results indicated the renal injury induced by meglucamine diatrizoate was alleviated by SMI. Conclusion: SMI could prevent renal tissue from contrast media induced nephropathy in SD rats. The effect may partially owe to its preventing intracellular calcium accumulation, inhibiting PLA2 activity and dilating renal vessels.

Study on the Protective Effect of Shengmai San(生脉散) on the Myocardium in the Type 2 Diabetic Cardiomyopathy Model Rat

Objective:To study the effect of Shengmai San(生脉散Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy(DCM) model.Methods:The DCM rat model was established by combination of insulin resistance induced by a high-fat diet with intraperitoneal injection of high dose streptozotocin(50 mg/kg).And these rat models were randomly divided into three groups:a normal group(n=12,one of them died),a model group(n=15) and a Shengmai San group(treatment group,n=15).The damage of the myocardium was assessed by electrocardiogram at the twelfth week after modeling,and the blood glucose,cholesterol and triglyceride levels were determined;the content of the left cardiac ventricle myocardial collagen was quantified by Masson staining test;the level of myocardial cell apoptosis was detected with TUNEL apoptosis detection kit;the damage extent of the myocardial sub-cellular structures was observed by electron microscopy;the expression levels of cardiac TSP-1(Thrombospondin-1),TGF-β1(Transforming Growth Ffactor-β) and TRB-3(Tribbles homolog 3) proteins were detected by immunohistochemical method;the expression levels of cardiac TSP-1,A-TGF-β1 and L-TGF-β1 proteins were detected by Western blotting;and the expression levels of TSP-1 and TRB-3 mRNAs were detected by real-time quantitative PCR.Results:Compared with the control group,the blood glucose,cholesterol,triglycerides levels in both the model groups and the Shengmai San group were significantly decreased;the myocardial tissue was less damaged and the collagen content was reduced in the Shengmai San group;the myocardial sub-cellular structure was injured to a lesser extent;the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and TSP-1,A-TGF-β1,L-TGF-β1 and chymase were decreased,and the expression levels of TSP-1 mRNA and TRB-3 mRNA were decreased in both the model groups and the Shengmai San group(the latter was better),.Conclusion:Shengmai San can inhibit myocardial fibrosis in the rat of diabetic cardiomyopathy,and significantly delay the formation of diabetic cardiomyopathy in hyperglycemia rats through multiple pathways.

Influence of Shengmai Capsule(生脉胶囊) on Recovery of Living Capacity in Patients after Myocardial Infarction

ABSTRACT Objective： To observe the effect of long-term application of Shengmai Capsule （生脉胶囊, SMC） on recovery of patients after myocardial infarction. Methods： A total of 120 myocardial infarction patients were assigned into two groups. Changes of angina pectoris, electrocardiogram （ECG）, living capacity and heart function in patients were observed after 6-month treatment. Results： The total effective rate in alleviating angina pectods was 90.0% and that in improving ECG figure was 93.3% in the treatment group, both were significantly higher than those in the control group, 73.4% and 70.0% respectively （P〈0.05）. The Karnofsky Performance Status scores of heart function were increased and the Activity of Daily Living scores in living capacity decreased in both groups, but the improvements were better in the treatment group （P〈0.01 and P〈0.05）. The parameters of cardiac function, including cardiac output, stroke volume, cardiac index and ejection fraction, were increased in both groups, but the increments in the treatment group were more significant （P〈0.01 or P〈0.05）. Conclusion： Long-term application of SMC could effectively prevent and treat angina pectoris, improve the living capacity and accelerate the recovery of heart function in patients after myocardial infarction.