Efficacy and Safety of Compound Danshen Dripping Pills Combined with Conventional Western Medicine in the Treatment of Coronary Heart Disease Complicated with Diabetes Mellitus:A Meta-Analysis / 中药新药与临床药理

Objective To systematically evaluate the efficacy and safety of Compound Danshen Dripping Pills combined with conventional western medicine in the treatment of coronary heart disease complicated with diabetes mellitus.Methods Wanfang database,CNKI,VIP,SinoMed,Cochrane Library,PubMed,Embase and Web of Science databases were searched to collect randomized controlled trials(RCTs)of Compound Danshen dripping pills combined with conventional western medicine in the treatment of coronary heart disease complicated with diabetes mellitus.The retrieval time is from the establishment of the database to May 2023.Two researchers independently completed literature screening,data collation and risk of bias evaluation.RevMan 5.4 software was used for Meta-analysis.Results Twenty-four RCTs with a total of 2 546 patients were included.Meta-analysis showed that the treatment of Compound Danshen Dripping Pills combined with conventional western medicine was better than that of conventional western medicine in improving the total effective rate of coronary heart disease complicated with diabetes mellitus[OR=4.93,95%CI(3.49,6.98),P＜0.000 01],plasma adiponectin[MD= 2.79,95%CI(2.30,3.27),P＜0.000 01],reducing fasting blood glucose[SMD=-1.06,95%CI(-1.24,-0.88),P＜0.000 01],postprandial two-hour blood glucose[MD=-1.53,95%CI(-1.71,-1.35),P＜0.000 01],glycosylated hemoglobin[MD=-1.56,95%CI(-2.01,-1.11),P＜0.000 01],homocysteine[MD=-8.47,95%CI(-8.89,-7.97),P＜0.000 01],low density lipoprotein[MD=-0.46,95%CI(-0.69,-0.24),P＜0.000 01],total cholesterol[MD=-0.45,95%CI(-1.11,-0.20),P=0.005],triglycerides[MD=-0.42,95%CI(-0.50,-0.34),P＜0.000 01],interleukin 6[SMD=-1.34,95%CI(-1.61,-1.07),P＜0.000 01],cardiovascular adverse events[OR=0.35,95%CI(0.19,0.64),P=0.000 6],incidence of adverse reactions[OR=0.45,95%CI(0.24,0.86),P=0.01].Conclusion Compound Danshen Dripping Pills combined with conventional western medicine in the treatment of coronary heart disease with diabetes mellitus is more effective than conventional western medicine treatment,and with better safety.However,due to the limit of the quality of the included studies and other factors,the above conclusions still need to be verified by more high-quality clinical trials.

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Network meta-analysis of five Chinese patent medicines in the treatment of coronary microvascular disease / 国际中医中药杂志

Objective:To evaluate the clinical efficacy rate, vascular endothelial relaxation factor NO and safety of five different Chinese patent medicines combined with western medicine in the treatment of coronary microvascular disease (CMVD).Methods:Randomized controlled trials (RCTs) of Shexiang Baoxin Pills, Tongxinluo Capsules, Compound Danshen Dripping Pills, Yindan Xinnaotong Soft Capsules, and Xinkeshu Tablets combined with conventional western medicine therapy in the treatment of CMVD were retrieved from China National Knowledge Infrastructure (CNKI), China Academic Journal Database (Wanfang Data), Chinese Science and Technology Journal Database (Chongqing VIP), China Biomedical Literature Service System (SinoMed), PubMed, Cochrance Library and Embase databases from the establishment of the database to June 2022. The literature was imported and screened by EndNote software, and the risk quality of literature bias was evaluated by Revman 5.4 software. StataSE16 (64-bit) software was used for reticular meta analysis to compare the differences in clinical efficacy and drug safety of five proprietary Chinese medicines combined with western medicine.Results:A total of 24 RCT studies were included, 24 of which were double-arm studies, and five kinds of proprietary Chinese medicine combined with western medicine were compared. The results of reticular meta analysis: in terms of improving the clinical effective rate, the order of the five proprietary Chinese medicine combination groups was as follows: Yindan Xinnaotong Soft Capsules group > Shexiang Baoxin Pills group > Tongxinluo Capsules group > Xinkeshu Tablets group > Compound Danshen Dripping Pills group. In terms of regulating vasodilation factor NO, the order of the four proprietary Chinese medicine combination groups is as follows: Yindan Xinnaotong Soft Capsules group > Compound Danshen Dripping Pills group > Tongxinluo Capsules group > Shexiang Baoxin Pills group. In terms of safety, there were 3 reports of adverse reactions in the research literature of the five proprietary Chinese medicines.Conclusions:The clinical efficacy rate of five kinds of proprietary Chinese medicine combined with western medicine routine regimen is better than that of western medicine routine regimen alone, and the combination group of four kinds of proprietary Chinese medicine is superior to western medicine in regulating vasodilation factor NO, and Yindan Xinnaotong Soft Capsules group is superior in clinical efficacy rate and regulation of vasodilation factor NO. However, the quality and samples of this study are different, and the comparison of the curative effect of the combined group of proprietary Chinese medicine still needs a large sample and high-quality RCT study to demonstrate.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial / 中国结合医学杂志

BACKGROUND@#Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.@*OBJECTIVE@#This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.@*METHODS@#This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.@*DISCUSSION@#This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Study on the improvement of Compound danshen tablets on blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats / 中国药房

OBJECTIVE To investigate the effect of Compound danshen tablet s o n improving the blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats. METHODS Sixty male SD rats were divided into normal group，model group ，simvastatin combined with （2S）-N-[N-（3，5-difluorophenylacetyl）-L-alanyl]-2-phenylglycine tert butyl （DAPT）group and low-dose ，medium-dose and high-dose groups of Compound danshen tablets ，with 10 rats in each group. Rats in the normal group received routine diet. The other 5 groups were intraperitoneally injected with 75％ yolk emulsion 10 mL/kg， fasting and drinking freely. After 16 h，they were fed high-fat diet for 4 weeks. Simvastatin combined with DAPT group was given simvastatin 0.002 g/kg and DAPT 0.012 g/kg at the same time of modeling. The low-dose ，medium-dose and high-dose groups of Compound danshen tablets were given Compound danshen tablets 0.25，0.5 and 1 g/kg respectively at the same time of modeling ， the normal group and model group were given equal volume of distilled water ，once a day ，for 4 weeks. The serum levels of total cholesterol（TC），triglyceride（TG），creatinine（Cr）and urea nitrogen （BUN）in serum were detected by biochemical method ； kidney coefficient of rats was calculated ；histopathological changes of rat kidney were observed by HE staining ，and the renal injury was scored according to the degree of renal tubular injury and glomerular sclerosis in renal cortex ；expression levels of Notch signal receptor 1（Notch 1），Notch signal ligand 1（Jagged1）and hairy division associated enhancer 1（Hes1）in kidney were detected by immunohistochemistry ；mRNA expressions of Notch 1，Jagged1 and Hes 1 in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Compared with normal group ，the serum levels of TG ， TC，Cr and BUN were increased significantly in model group （P＜0.05）；renal coefficient increased significantly （P＜0.05）； pathological changes occurred in renal tissue ，and the scores of renal tubular injury and glomerular sclerosis increased significantly （P＜0.05）；protein and mRNA expressions of Notch1， Jagged1， Hes1 in renal tissue were increased significantly（P＜0.05）. Compared with model group ，serum levels of TG ，TC，Cr and BUN ，renal coefficient ，the scores of renal tubular injury and glomerular sclerosis ，protein and mRNA expression of Notch 1，Jagged1 and Hes 1 in renal tissue were all decreased in low-dose ，medium-dose and high-dose groups of Compound danshen tablets （P＜0.05），and most indexes showed a dose-dependent trend ；the degree of renal lesions was reduced. CONCLUSIONS Compound danshen tablets possess obvious hypolipidemic effect ，and can protect the renal function of hyperlipidemia model rats by down-regulating Notch 1/Jagged1 signal pathway.

Research on batch-to-batch quality control of compound Danshen extract based on physical characterization and multivariate statistical analysis / 中国中药杂志

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.

Systematic review and Meta-analysis of 26 randomized controlled clinical trials of Compound Danshen Dripping Pill for non-proliferating diabetic retinopathy / 中草药·英文版

Objective: Diabetic retinopathy (DR) is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion. Non-proliferating diabetic retinopathy (NPDR) is the early stage of DR. It eventually occurs to some degree in all patients with diabetes mellitus. In recent years, many clinical trials have shown that Compound Danshen Dripping Pill (CDDP) may be associated with the improvement of NPDR symptoms. The aim of this study was to quantitatively summarize the association between CDDP and the therapeutic effects of NPDR. Methods: It was conducted that a systematic literature search of PubMed, Web of Science, CNKI, VIP and Wanfang Data updated in June 2020 with the following search terms: “diabetic retinopathy” or “retinopathy” or “DR” or “NPDR”, in combination with “Compound Danshen Dripping Pill” or “Salvia miltiorrhiza” or “Danshen”. Risk ratio (RR) and weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between treatment and control groups. The sensitivity analyses were undertaken by removing each individual study when high heterogeneity appeared. Subgroup analysis, Meta-regression, and publication bias analysis were also conducted. The strength of evidence was evaluated with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Results: Twenty-six RCTs involving 2047 subjects were included to conduct a Meta-analysis after screening the studies, extracting the data, and assessing the study quality. The Stata15.0 software was utilized for processing. Meta-analysis indicated that curative effects of treatment group with CDDP was significantly better than control [RR = 0.54, 95% CI (0.40, 0.73); moderate-quality evidence]. In addition, the results showed that CDDP was significantly associated with improving retinal hemorrhages [WMD = −0.62, 95% CI (−0.78, −0.46); low-quality evidence], the vision [WMD = 0.14, and 95% CI (0.09, 0.19), low-quality evidence], fundus fluorescence angiography [RR = 0.37 and 95% CI (0.23, 0.60); low-quality evidence], reduction of retinal microaneurysm [WMD = −3.74 and 95% CI (−4.38, −3.11); moderate-quality evidence], hemangioma volume [WMD = −3.15, 95%CI (−3.45, −2.85); moderate-quality evidence], macular thickness [WMD = −5.52, 95%CI = (−64.27, −48.78); low-quality evidence], mean defect [WMD = −1.65 and 95% CI (−1.95, −1.34); very low-quality evidence], fasting blooding glucose [WMD = −0.95, 95% CI (−1.19, −0.70); low-quality evidence), hemoglobin A1c [WMD = −0.62, 95% CI (−0.93, −0.30); low-quality evidence], high sensitive C reaction protein [WMD = −5.66, 95% CI (−8.01, −3.31); low-quality evidence]. Sensitivity, subgroup, and Meta-regression analyses were also assessed. Conclusion: The study demonstrated that CDDP has beneficial clinical effects for treating NPDR and improve the vision. Moreover, it indicated that oral CDDP in NPDR patients led to significant regulation of serum level of fasting blooding glucose, hemoglobin A1c and high sensitive C reaction protein, which was associated with the pathogenesis of NPDR. However, high-quality and large randomized clinical trials will be needed to prove the consequence in future.

Effects of Compound Danshen Dripping Pills on Contrast-induced Nephropathy after Percutaneous Coronary Intervention and Patients ’Prognosis / 中国药房

OBJECTIVE：To observe the effects of Compound danshen drip ping pills on the prevention of contrast-induced nephropathy（CIN）after percutaneous coronary intervention （PCI）and its influence on clinical prognosis. METHODS ：From Jan. to Jun. 2020，240 patients with coronary heart disease receiving PCI in Tianjin Chest Hospital were randomly divided into control group（120 cases）and Danshen dripping pills group （120 cases）according to random number table. The patients in both groups were injected with Lippaclitanol injection 1-5 mL slowly through radial or femoral artery sheath ，and intravenous hydration was performed before and after PCI ；Danshen dripping pills group was additionally given Compound danshen dripping pills 270 mg orally for a long term ，three times a day ，three days before and after PCI ，on the basis of the control group. The levels of renal function indexes [serum creatinine （Scr），blood urea nitrogen （BUN），cystatin C （Cys-C），creatinine clearance rate （Ccr）]， inflammatory reaction indexes [high sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）] and oxidative stress index [malondialdehyde （MDA）] were observed in 2 groups before and 72 hours after PCI. The occurrence of CIN in 2 groups was recorded 3 days after PCI therapy ；the occurrence of major cardiovascular adverse events was also observed during 1-year follow-up period. RESULTS ：Before treatment ，there was no significant difference in serum renal function indexes ，inflammatory reaction indexes and oxidative stress index between 2 groups（P＞0.05）. Seventy-two hours after PCI ，serum levels of Scr ，BUN， Cys-C，hs-CRP，IL-6 and MDA were increased significantly in 2 groups than before treatment ，while the Ccr were decreased significantly；those indexes of Danshen dripping pills group were significantly better than those of control group （P＜ 0.05）. The incidence of CIN in Danshen dripping pills group was 4.2％ after treatment ， and total incidence of major cardiovascular adverse events was 13.3％ during follow-up period，which were sign ificantly lower than 13.3％ and 27.5％ of control group （P＜0.05）. CONCLUSIONS ：Compound danshen dripping pills may have a certain effect on the prevention of CIN in coronary heart disease patients after PCI ，and can reduce the incidence of major cardiovascular adverse events.

Meta-analysis of the Effectiveness and Safety of Compound Danshen Dripping Pills in Improving Aspirin Resistance / 中国药房

OBJECTIVE：To systematically evaluate the effectiveness and safety of Compound danshen dripping pills in improving aspirin resistance ，and to provide evidence-based evidence for clinical drug use. METHODS ：Retrieved from CNKI ， VIP，Wanfang database ，CBM，PubMed，Embase，the Cochrane L ibrary，randomized controlled trials （RCTs）about Compound danshen dripping pills （trial group ）versus aspirin （control group ）were collected during the inception to Jun. 2020. After literature screening and data extraction ，bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literatures ，and Rev Man 5.3 software was used for Meta-analysis and publication bias analysis. RESULTS ：A total of 10 RCTs were included ，with a total of 800 patients. Meta-analysis showed that the platelet aggregation rate （PAR）induced by adenosine diphosphate （ADP）in trial group was significantly lower than that of control group [SMD ＝－2.63，95％CI（－3.56，－1.70），P＜0.000 01]. Results of sub-group analysis by treatment cycle showed that PAR induced by ADP in trial group after 2 weeks of treatment [SMD ＝－2.11，95％CI（－2.75，－1.46），P＜0.000 01]，4 weeks of treatment [SMD ＝－2.84，95％CI（－4.26，－1.41），P＜0.000 1] Δ 基金项目 ：国家重点研发计划中医药现代化研究重点专项 and 8 weeks of treatment [SMD ＝－2.63，95％CI（－3.21， （No.2019YFC1710000，No.2019YFC1710003）；国家中医药管理局中 － 2.04），P＜0.000 01] was significantly lower than control 医药循证能力建设项目（No.2019XZZX-XXG003）；河南省创新型科技 团队项目 group. PAR induced by arachidonic acid （AA）of trial group ＊硕士研究生 。研究方向：中西医结合心血管疾病的预防和治 was significantly lower than that of control group [SMD ＝ 疗。E-mail：guohongxin1214@163.com －2.44，95％CI（－3.64，－1.24），P＜0.000 1]. Results of # 通信作者：主任医师，教授，硕士生导师，博士。研究方向：中医 sub-group analysis by treatment cycle showed that PAR 药防治心血管疾病的临床和基础 。电话：0371-66233478。E-mail： induced by AA in trial group after 2 weeks of tre atment [SMD ＝ zhumingjun317@163.com －2.56，95％CI（－3.26，－1.85），P＜0.000 01]，4 weeks of 中国药房 2021年第32卷第6期 China Pharmacy 2021Vol. 32 No. 6 ·743· treatment of [SMD ＝－2.45，95％CI（－4.79，－0.10），P＝0.04]，8 weeks of treatment [SMD ＝－2.38，95％CI（－2.94，－1.82），P＜ 0.000 01] was significantly lower than control group. The decrease of ADP-induced PAR [SMD ＝2.24，95％CI（1.36，3.13），P＜ 0.000 01]，AA-induced PAR [SMD ＝2.42，95％CI（1.94，2.89），P＜0.000 01] and response rate [RR ＝8.56，95％CI（4.38，16.74）， P＜0.000 01] in trial group were significantly higher than control group ，while the incidence of ADR [RR ＝0.30，95％CI（0.15， 0.60），P＝0.000 6]，the incidence of ischemic events [RR ＝0.13，95％CI（0.07，0.27），P＜0.000 01]，CR and RF after treatment （P＜0.05）were significantly lower than control group. There was no statistical significant difference in the incidence of bleeding events between 2 groups [RR ＝0.78，95％ CI（0.34，1.78），P＝0.55]. The results of publication bias showed that there was less possibility of publication bias in this study. CONCLUSIONS ：Compound danshen dripping pills can effectively improve aspirin resistance and has good safety.

Systematic review of efficacy and safety of Compound Danshen Injection combined with Western medicine in treatment of vascular dementia / 中国中药杂志

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.

Meta-analysis of clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in treatment of hypertensive left ventricular hypertrophy / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy. China National Knowledge Infrastructure(CNKI), Wanfang, VIP, PubMed, EMbase, Cochrane Library, Ovid and Web of Science databases were searched by computer to retrieve the randomized controlled trials(RCTs) of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy from the establishment of databases to July 2020. After two researchers performed data retrieval, data extraction, and risk assessment of bias, they used RevMan 5.3 software for Meta-analysis. A total of 10 RCTs were included, with a total of 979 patients. Meta-analysis results showed that in terms of interventricular septal thickness(MD=-0.70, 95%CI[-1.15,-0.24], P=0.003), left ventricular posterior wall thickness(MD=-0.81, 95%CI[-1.41,-0.21], P=0.008), left ventricular mass index(MD=-8.75, 95%CI[-17.40,-0.10], P=0.05), systolic blood pressure(MD=-8.97, 95%CI[-13.46,-4.48], P<0.000 1), diastolic blood pressure(MD=-5.87, 95%CI[-8.39,-3.34], P<0.000 01) and left ventricular end-diastolic diameter(MD=-1.73, 95%CI[-2.38,-1.08], P<0.000 01), Compound Danshen Dripping Pills combined with conventional antihypertensive drugs was superior to conventional antihypertensive drugs. In terms of left ventricular ejection fraction(MD=0.41, 95%CI[-0.74, 1.55], P=0.49), there was no statistical difference in treatment between the two groups. Because of the small amount of literatures included in the safety aspect, it is impossible to give an accurate conclusion. The GRADE score showed that the level of evidence was low and extremely low. The results show that the Compound Danshen Dripping Pills combined with conventional antihypertensive drugs may effectively improve the clinical efficacy for hypertensive ventricular hypertrophy, and the safety needs to be further explored. Due to the low quality of the included literatures, more high-quality RCTs are needed for verification.

Protective Effect of Huoxue Dingtong Prescription on Myocardial Ischemia Reperfusion Injury in Animal Model Based on NF-κB Signal Pathway / 中国实验方剂学杂志

Objective::To explore the protective effect of Huoxue Dingtong prescription on myocardial ischemia reperfusion injury in animal model based on nuclear transcription factor-κB(NF-κB) signal pathway. Method::In compound Danshen dropping pill group, SD rats were randomly divided into sham group, model group, compound salvia miltiorrhiza dropping pill group, high-dose Huoxue Dingtong group low-dose Huoxue Dingtong group, high-dose Huoxue Dingtong+ NF-κB inhibitor group. The rats in each group were administered continuously for 2 weeks. The rats in high-dose Huoxue Dingtong group+ pyrrolidine dithiocarbamate(PDTC) group were intraperitoneally administered the next day after modeling. Injection with PDTC and ligation of anterior descending branch of left coronary artery were performed to detect left ventricular function and Na+ -K+ -ATPase activity. Blood was collected from each animal abdominal aorta, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum creatine kinase isoenzyme (CK-MB), troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), superoxide gasification enzyme (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px). Western blot was used to detect the expressions of NF-κB, NF-κB inhibitor α (IκBα) and IκB kinase(IκκB) in myocardium. Result::Compared with model group, compound Danshen dropping pill group, high-dose Huoxue Dingtong group and low-dose Huoxue Dingtong group could reduce serum CK-MB, cTnT, TNF-α, IL-6, IL-1β, MDA, increase SOD and GSH-Px contents, increase the protein expressions of IκBα and IκB in myocardial tissue, and increase the activity of Na+ -K+ -ATPase in myocardial energy metabolism in myocardial ischemia-reperfusion model rats (P<0.05). However, high-dose Huoxue Dingtong group+ PDTC did not decrease serum CK-MB, cTnT, TNF-α, IL-6, IL-1β and MDA, increase SOD, GSH-Px, and increase the protein expression levels of IκBα and IκκB in myocardial tissue. There was no significant difference between high-dose Huoxue Dingtong group+ PDTC and model group. Conclusion::Huoxue Dingtang prescription can inhibit the activation of NF-κB signaling pathway, reduce the expression of inflammatory mediators and the production of free radicals, and increase the activity of Na+ -K+ -ATPase in the process of myocardial energy metabolism by up-regulating the expressions of IκBα and IκκB proteins in myocardial tissue of myocardial ischemia-reperfusion model.

Meta analysis on efficacy of Compound Danshen Dropping Pills in treating angina based on syndrome differentiation / 中草药

Objective: To evaluate the efficacy and safety of the combination therapy of Compound Danshen Dropping Pills and conventional chemical drugs in the treatment of the angina by Meta-analysis. Methods: Databases including CNKI, WanFang, CBM, VIP, PubMed, and Cochrane Library were searched to collect qualified researches, and the quality of articles was evaluated according to Cochrane Handbook. Meta-analysis including subgroup analysis was performed by using Stata 13.1 and RevMan 5.3 software. All these methods were used to systematically evaluate the safety and clinical efficacy of Compound Danshen Dropping Pills in the treatment of angina pectoris under two circumstances (with or without syndrome differentiation). Results: A total of 39 studies involving 3 941 patients were studied, including 1 991 patients in the experimental group and 1 950 in the control group. The results of Meta analysis showed that: the clinical efficacy [RR = 1.24, 95%CI (1.20, 1.28), P < 0.000 01], ECG efficacy [RR = 1.29, 95%CI (1.21, 1.37), P < 0.000 01], angina attack frequency [WMD = -1.82, 95%CI (-3.28, -0.36), P = 0.01], duration of angina attack [WMD = -2.09, 95%CI (-2.67, -1.50), P < 0.000 01], hs-CRP [WMD = -2.63, 95%CI (-4.39, -0.86), P = 0.003], ET [WMD = -16.22, 95%CI (-19.37, -13.06), P < 0.000 01], platelet aggregation [WMD=-7.46, 95%CI (-11.15, -3.78), P < 0.000 1], GMP-140 [WMD=-5.64, 95%CI (-6.88, -4.39), P < 0.000 01] and fibrinogen [WMD = -0.73, 95%CI (-1.00, -0.46), P < 0.000 01] of routine western medicine treatment combine with Compound Danshen Dripping Pills group had significant difference compared with the control group; In terms of clinical efficacy, the combination effect of dialectical medication group and non dialectical medication group had no significant difference (P = 0.55, I2 = 0). A total of 15 studies described adverse reactions, with 43 cases in the experimental group and 65 cases in the control group. There was no significant publication bias on funnel plot and Egger's test. Conclusion: It is safe and effective to use Compound Danshen Dropping Pills in patients with coronary heart disease and angina, which can further improve the clinical effect compared with the simple routine treatment. There is no significant difference between the therapeutic effect of Compound Danshen Dropping Pills and that of non-syndrome differentiation. However, these conclusions still need to be verified with more high-quality and large-sample literature.

Electrostatic dry powder coated moisture barrier films for Compound Danshen Tablets / 中草药

Objective: Using ultrafine hydroxypropyl cellulose (HPC) powders as coating material to prepare moisture barrier coating film for Compound Danshen Tablets by an innovative electrostatic powder coating technology. The effects of coating prescription and process parameters on coating efficiency and coating film properties were investigated, so as to provide new ideas for moistureproof coating of moisture sensitive traditional Chinese medicine such as Compound Danshen Tablets. Methods: Free films were prepared by applying an electrostatic deposition process, and the effects of liquid plasticizer on the mechanical properties and the water vapor permeability were investigated. And the Compound Danshen Tablets were dry coated with ultrafine powders by the electrostatic coating technology. The effects of coating formulations and processing conditions on the moisture sorption behavior of the barrier film coated tablets were studied. Results: The coating efficiency could be manipulated by adjusting the charging voltage of the electrostatic spray gun and the amount of the liquid plasticizer. Compared with static curing process, dynamic curing process was capable to produce a satisfactory film with an enhanced moisture barrier function for the herbal medicines. The best coating process parameters were plasticizer spraying time 3 min and titanium dioxide addition ratio 1%. The minimum hygroscopicity was achieved when the coating level was increased to 6.7%. Conclusion: The moisture-protective effect by using a novel electrostatic coating technology with ultrafine powders was efficiently achieved, suggesting that it was a promising alternative for the protection for the moisture sensitive drugs.

Effect of compound Danshen dripping pills on expression of miR-1 in serum after percutaneous coronary intervention in patients with acute myocardial infarction / 中国中西医结合急救杂志

Objective To explore the effects of compound Danshen dripping pills on the expression levels of micro RNA-1 (miR-1) and inflammatory factors in serum of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Methods A total of 180 AMI patients admitted to Mindong Hospital of Ningde City from March 2017 to October 2018 were divided into a compound Danshen dripping pills group and a conventional western medicine treatment group, 90 cases in each group. According to the disease situations of all the patients, they needed to undergo PCI treatment, after the intervention, in the conventional western medicine treatment group, aspirin enteric-coated tablet (metformin hydrochlorid) was given as the basic anti-coagulation medicine and in the compound Danshen dripping pill group, on the basic treatment, 10 Danshenn pills each time, 3 times a day, were orally applied. Both groups were evaluated for efficacy after 2 months of continuous treatment. Echocardiography was used to detect the patients' cardiac functions; the changes of the expression levels of serum miR-1, interleukins (IL-1, IL-6), tumor necrosis factor-α (TNF-α), and myocardial troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) in the two groups before and after treatment were observed. Results After treatment in both groups, the left ventricular ejection fraction (LVEF) and cardiac output index (CI) were significantly higher than those before treatment, while the expression of miR-1 and serum IL-1, IL-6, TNF-α, cTnI and CK-MB were lower than those before treatment, the LVEF and CI in the compound Danshen dripping pill treatment group were obviously higher than those in the conventional western medicine treatment group [LVEF: 0.60±0.08 vs. 0.56±0.08, CI (L·min-1·m-2): 6.02±0.34 vs. 4.91±1.50, both P < 0.05], the expression level of miR-1 and serum IL-1, IL-6, TNF-α, cTnI and CK-MB in the compound Danshen dripping pill group were lower than those in the conventional western medicine treatment group [miR-1 (2-ΔΔCt): 0.69±0.17 vs. 0.85±0.22, IL-1 (μg/L): 59.20±18.67 vs. 68.31±23.69, IL-6 (μg/L): 20.36±1.87 vs. 25.38±2.39, TNF-α (μg/L): 28.65±1.63 vs. 31.86±2.92, cTnI (μg/L):3.12±0.88 vs. 4.03±0.97, CK-MB (U/L): 29.18±10.52 vs. 34.28±10.21, all P < 0.05]. Conclusion Compound Danshen dripping pills can reduce serum the expression levels of miR-1 and inflammatory cytokines in patients with AMI after PCI.

Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β1 by miRNA-200b / 中国实验方剂学杂志

Objective: To study the protective effect and mechanism of compound Danshen dropping pills on the heart of rats with type 2 diabetic cardiomyopathy. Method: Seventy-five male SD rats were randomly divided into blank group (15 rats) and model group (60 rats). The model group was fed with high-sugar and high-fat diet, high-sugar and high-fat milk and sucrose water. Six weeks later, rats with foodborne obesity (body mass ≥ the mean body mass of blank control group + 2 times standard deviation) were selected and intraperitoneally injected with 1% streptozotocin (STZ)28 mg·kg-1. After 12 weeks, rats with fasting blood glucose ≥ 11.1 mmol·L-1 and polydipsia, diuresis, polyphagia and weight loss were randomly divided into model group, compound Danshen dropping pills group (0.5 g·kg-1) and metformin group (0.5 g·kg-1) and intervened for 12 weeks. At the end of the experiment, echocardiography was used to evaluate cardiac function. Blood samples were taken to determine the corresponding biochemical indicators of rats. Histopathological changes of myocardium were observed by hematoxylin-eosin (HE) and Masson staining. The ultrastructure of myocardium was observed under electron microscope. Western blot was used to detect the expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-β1) and type Ⅰ collagen (Collagen Ⅰ). Real-time fluorescence quantitative analysis (Real-time PCR) was used to detect the expression of miRNA-200b. Result: Compared with the blank group, the heart weight index (HMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterin(LDL-C) levels in the model group were significantly increased (PPPPPβ1 and Collagen I increased (PPPPPPβ1 and Collagen I was decreased (PPConclusion: Compound Danshen dropping pills may play a protective role in the heart of type 2 diabetic cardiomyopathy rats by lowering lipid, up-regulating the expression of miR-200b and inhibiting the expression levels of VEGF, TGF-β1 and Collagen I.

Bioassay method for Compound Danshen Tablets based on a platelet aggregation inhibition test / 药学学报

A bioassay method for inhibiting platelet aggregation in vitro was established to quantify the pharmacological effects of Compound Danshen Tablets and support its quality control. The inhibition of platelet aggregation in rabbit plasma in vitro by Compound Danshen Tablets was used as the experimental system. The titer was calculated by using the method of dose-response parallel lines. As a result, a bioassay for the inhibition of platelet aggregation in vitro by Compound Danshen Tablets was established. Linearity was good in the concentration range of 0.128 g·mL-1 to 0.205 g·mL-1, and the titer of standard Compound Danshen tablets was 7 659 U·g-1 according to the titer definition. This in vitro assay was simple, reliable, reproducible and convenient. The activity of Compound Danshen Tablets in inhibiting platelet aggregation was quantified by potency assay and the quality of different batches was evaluated. The method can be applied for the quality control of Compound Danshen Tablets.

Dissolution kinetics of Compound Danshen Tablets based on cell bioelectrical sensing effect / 中草药

Objective: Establishing the model of cell bioelectrical sensing effect of Compound Danshen Tablets to study its dissolution kinetics. Methods: By means of real-time cell-based assay, the in vitro dissolution of Compound Danshen Tablets can be investigated, and then the dissolution kinetics model can also be established. In addition, the result was compared and verified by UV-Vis. Results: The cell line with specific dependence on Compound Danshen Tablets was screened by CCK-8 experiment and RTCA experiment. The dissolution kinetics model of Compound Danshen Tablets based on RTCA technology was established, and the best fitting model was obtained: Weibull model ln{ln[1/(1-Q)] =1.071 4 lnt-3.736 7; Establish a dissolution kinetic model of Compound Danshen Tablets based on UV spectrophotometry to obtain the best fitting model, Weibull model ln{ln[1/(1-Q)]}=1.080 4 lnt-3.723 4; Comparing the two Weibull models, the RTCA fitted model worked better. Conclusion: The application of RTCA in the dissolution kinetics of traditional Chinese medicine compound solid preparations is feasible, Which provides new ideas for traditional Chinese medicines and the quality evaluation of traditional Chinese medicine compunds.

Comparison of efficacy and mechanism of Compound Danshen Tablets and its decomposed prescriptions on learning and memory ability of rats with vascular dementia / 中草药

Objective: To compare the effect and mechanism of Compound Danshen Tablets and its disassembled prescription on learning and memory ability of rats with vascular dementia (VD). Methods: Rats with normal learning and memory ability were screened through the shuttle box, and then divided into seven groups: sham group, model group, contrast group (dihydroergotaminemesylate 0.65 g/kg), Danshen group (ethanol extract of Salvia miltiorrhiza 0.3 g/kg), Senqi group (Panax notoginseng powder 0.3 g/kg), Compound Danshen Tablets group (low dose 0.3 g/kg, high dose 0.6 g/kg), ig administration, once daily one time, after 7 d of continuous administration, the VD rat model was established by bilateral common carotid artery ligation and reperfusion. After 7 d of continuous administration, the shuttle box test and neurological deficit score were performed; TTC staining and Nissl staining were used to detect the area of cerebral ischemia and the pathological changes of rat in the cerebral cortex respectively. The changes of SOD, MDA, Ach, 5-HT in the brain and VEGF, ET, eNOS, IL-6 in the serum were detected by kit. Results: Compared with the model group, the Compound Danshen Tablets group increased the number of conditional stimulation avoidance in VD rats, reduced the neurological function score and cerebral ischemia area, and reduced the MDA in rat brain tissue and ET, eNOS, IL-6 in rat serum, and increased Ach, 5-HT, SOD in the brain and VEGF in the serum. S. miltiorrhiza extract had better performance in reducing MDA in rat brain tissue and ET, eNOS, IL-6 in rat serum, SOD in the brain than in P. notoginseng; P. notoginseng was more advantageous in improving the content of Ach and 5-HT in rat brain tissue. The high-dose group of Compound Danshen Tablets had significant differences in SOD, MDA, ACH, 5-HT, and VEGF compared with Danshen group or Senqi group (P < 0.05, P < 0.01). Conclusion: Compound Danshen Tablets can improve the cognitive learning and memory ability of VD rats. The mechanism maybe enhance the secretion of Ach by the central cholinergic nervous system, improve the content of the monoamine neurotransmitters 5-HT in the hippocampus and hypothalamus, reduce the lipid peroxidation damage of the brain tissue, inhibit the inflammatory injury reaction and promote angiogenesis. In the compound, S. miltiorrhiza extract as the role of “Jun medicine”, plays a major role, while P. notoginseng assists “Jun medicine” in treating VD.