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.

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.

Improvement of myocardial fibrosis injury by Shengmai injection in ischemia-induced heart failure in a rat model

Background:Heart failure(HF)is the leading cause of death worldwide.Myocardial infarction(MI)is a major contributor to HF.Shengmai injection(SMI)has exhibited protective efficacy in preventing HF.However,the advantages of SMI in the progression of MI-induced HF remain unclear.Objective:To reveal the advantages of SMI in the progression of MI-induced HF.Methods:The differently expressed proteins in rat models with ischemia at the 7th,14th,21st,and 28th days were obtained from PubMed.The“compound-target”network of SMI was constructed via the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine database.The protein-protein interaction relationship was constructed,and biological function was applied to evaluate the advantage effect of SMI in the progression of MI-induced HF.In addition,the prediction results were validated in rats with left anterior descending coronary artery ligation.The cardiac function and heart performance were observed via echocardiography,hematoxylin-eosin staining,and Masson staining,and the levels of procollagen type I carboxy-terminal propeptide,recombinant versican(VCAN),and collagen 1A1(COL1A1)weremeasured via enzyme-linked immunosorbent assay in rat plasma.In vitro,H9c2 cells were treated with Angiotensin II(Ang II),and the cell viability,the level of reactive oxygen species(ROS)and Ca^(2+),and the expression of ANP and connective tissue growth factor were evaluated.Furthermore,the schizandrin A was identified as one of the possible key compounds.After schizandrin A treatment,the level of ROS and Ca^(2+)and the expression of COL1A1 and VCAN were evaluated.Results:There were 189 compounds and 1612 targets involved in the“compound-target”network,and an interaction relationship was constructed.According to the top subnetwork,the Gene Ontology annotation revealed that SMI may have an antifibrotic and cardiac protective effect against MI-induced HF.In rats,SMI increased ejection fraction,left ventricular fractional shortening,and cardiac output and decreased fibrosis injury;moreover,SMI decreased the levels of procollagen type I carboxy-terminal propeptide,VCAN,and COL1A1 within 35 days.When compared with the Ang II treatment group,SMI increased cell viability and decreased cellular calcium concentration,ROS generation,and the expression of ANP and connective tissue growth factor in vitro.Furthermore,schizandrin A was discovered to be a possible compound in myocardial protection.Schizandrin A increased cell viability after Ang II treatment while decreasing COL1A1 and VCAN levels.Conclusions:This method demonstrates that SMI has an antifibrotic effect.This study provides a promising perspective on translating omics data to clinical applications,as well as an appealing approach to investigating the precise intervention of a multicomponent drug.

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.

Mechanism of Shengmai Injection on Anti-Sepsis and Protective Activities of Intestinal Mucosal Barrier in Mice

Objective:To study the mechanism of Shengmai Injection(SMI)on anti-sepsis and protective activities of intestinal mucosal barrier.Methods:The contents of 11 active components of SMI including ginsenoside Rb1,Rb2,Rb3,Rd,Re,Rf,Rg1,Rg2,ophioposide D,schisandrol A and schisantherin A were determined using ultra-performance liquid chromatography.Fifty mice were randomly divided into the blank,the model,the low-,medium-and high-dose SMI groups(0.375,0.75,1.5 mL/kg,respectively)by random number table,10 mice in each group.On SMI group,SMI was administrated to mice daily via tail vein injection for 3 consecutive days,while the mice in the blank and model groups were given 0.1 mL of normal saline.One hour after the last SMI administration,except the blank group,the mice in other groups were intraperitoneally injected with lipopolysaccharide(LPS)saline solution(2 mL/kg)at a dosage of 5 mL/kg for development of endotoxemia mice model.The mice in the blank group were given the same volume of normal saline.Inflammatory factors including interferon-γ(INF-γ),tumor necrosis factor-α(TNF-α),interleukin(IL)-2 and IL-10 were measured by flow cytometry.Myosin light-chain kinase(MLCK),nuclear factorκB(NF-κB)levels,and change of Occludin proteins in jejunum samples were analyzed by Western blot.Results:The decreasing trends of INF-γ,TNF-α and IL-2 were found in serum of SMI treatment groups.In SMI-treated mice,the content of Occludin increased and MLCK protein decreased compared with the model group(P<0.05 or P<0.01).The content of cellular and nuclear NF-κB did not change significantly(P>0.05).Conclusion:SMI may exert its anti-sepsis activity mainly through NF-κB-pro-inflammatory factor-MLCK-TJ cascade.

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.

Effect of Shengmai Injection(生脉注射液) on Diaphragmatic Contractility in Doxorubicin-Treated Rats

Objective：To explore the diaphragmatic toxicity in doxorubicin（DOX）-treated rats and the related mechanisms,as well as the effects of Shengmai Injection（SMI,生脉注射液）on the diaphragmatic dysfunction.Methods：Thirty Sprague-Dawley male rats were randomly divided into three groups：control,DOX-treated and DOX＋SMI treated groups.DOX was given to rats in DOX and DOX＋SMI groups in 6 equal doses[2.5 mg/kg,intraperitoneal injection（i.p.）],on alternate days,over a period of 2 weeks for a cumulative dose of 15 mg/kg.SMI was given to DOX＋SMI rats in 12 doses（3 mL/kg,i.p.）for a period of 2 weeks before the administration of DOX and 2 weeks during the administration of DOX.The rats in the control group received equal volume of normal saline.Subsequently,the twitch and tetanic characteristics and force-frequency relationships,and the malondialdehyde（MDA）levels and the superoxide dismutase（SOD）activities,as well as the mRNA content and proteins of inducible nitric oxide synthase（iNOS）were determined.Results：The DOX-treated rats had decreased the peak twitch tension（Pt）,maximal tetanic tension（P0）and force-frequency relationship as compared with the control rats（P〈0.01）,while the diaphragm contractility in rats treated with SMI were significantly higher than that in DOX-treated rats（P〈0.01）.The DOX-treated rats had increased MAD levels and decreased SOD activities（P〈0.05）,and SMI decreased the MDA levels and increased the SOD activities in DOX-treated rats（P〈0.05）.Ultrastructure of diaphragm in the DOX-treated rats revealed typical alterations including fracture of diaphragm fibers,and edema and degeneration of mitochondria;these changes were relieved by SMI treatment.The mRNA content and protein of iNOS in DOX-treated rats were remarkably higher than those in control rats（P〈0.01）,while SMI decreased the mRNA expression level of iNOS in DOX-treated rats（P〈0.05）.Conclusions：Lipid peroxidation is responsible for DOX-induced diaphragm toxicity.SMI protects diaphragm muscles and their function from DOX impairment,and these beneficial effects may be somehow correlated with the decrease in expression of iNOS and lipid peroxidation.

The rapeutic Effect of Sheng mai Injection (生脉注射液) on Respiratory Functionin Chronic Obstructive Pulmonary Disease

Objective: To explore the therapeutic effect of shengmai injec tion (SMI) on respiratory function in chronic obstructive pulmonary disease (COPD ).Methods: Twenty patients with COPD were continuously treated w ith SMI by intravenous drip for 14 days and their lung vital capacity (VC),for ced vital capacity (FVC),forced vital capacity of the first second (FEV1),FEV1/FVC , maximum voluntary ventilation (MVV), maximum inspiratory pressure (MIP),load respiratory time (LT), 6 minute walk distance (6 MWD), arterial blood gas an alysis, and Borg dyspnea scale were examined respectively before and after treatment a nd compared before and after treatment or with the control group.Results: After treatment all parameters in the treated group were significantly better than those in the control group or than those before treatment (P<0.05) with the exception of FVC and FEV1/FVC. Conclusion: SMI could improve respiratory function in COPD. So i t is an effective rehabilitative injection in treating COPD