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.

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).

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms / 中国结合医学杂志

Qishen Yiqi Dripping Pills (QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside IV, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

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.

Fufang Danshen dripping pills protect vascular smooth muscle cells by reducing endoplasmic reticulum stress and autophagy through regulating IRE1-TRAF2-ASK1 -JNK pathway / 中国药理学通报

Aim To investigate the molecular mechanism of the protection of vascular smooth muscle cells by the regulation of endoplasmic reticulum stress and autophagy by Fufang Danshen dripping pills.Methods Fifty patients with atherosclerosis were randomly divided into two groups; one group received normal treatment,while the other group was added Fufang Danshen dripping pills,and the clinical efficacy was observed.Vascular smooth muscle cells were divided into control,ox LDL model,Fufang Danshen dripping pill group,Fufang Danshen dripping pill+endoplasmic reticulum stress inhibitor group,and Fufang Danshen dripping pill+endoplasmic reticulum stress inducer group.Proliferation was detected,and vasodilator function factors and oxidative stress were measured in each group,ER stress marker proteins,autophagy marker proteins and apoptosis related protein expression were detected,and activation of the IRE1-TRAF2-ASK1-JNK signaling pathway was detected.Results Compared with control group,various indicators of cells in ox-LDL model group showed that they were under ER stress,high oxidative stress,high autophagy status,and the IRE1-TRAF2-ASK1-JNK pathway was found to be over activated.However,compared with ox LDL model group,the above indicators in Fufang Danshen dripping pill group and Fufang Danshen dripping pill+endoplasmic reticulum stress inhibitor group were significantly better,the IRE1-TRAF2-ASK1-JNK pathway was over activated,and the endoplasmic reticulum stress inhibitor was more obvious,and Fufang Danshen dripping pill+endoplasmic reticulum stress inducer group significantly reversed the improved effects of Fufang Danshen dripping pills.Conclusions Fufang Danshen dripping pills protect vascular smooth muscle cells by inhibiting excessive activation of the IRE1-TRAF2-ASK1-JNK pathway,decreasing endoplasmic reticulum stress,maintaining proper autophagy,and inhibiting abnormal cell proliferation and apoptosis.

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.

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 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.

Determination of five saponins in Xuesaitong Dropping Pills by micellar electrokinetic chromatography and evaluation method of between-batch consistency / 中国中药杂志

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) β-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 μm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.

Molecular mechanism of Qishen Yiqi Dripping Pills in treating myocardial ischemia:a study based on HIF-1 signaling pathway / 中国中药杂志

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.

Effect of dripping pills on coronary microcirculation disorder and cardiac dysfunction in a porcine model of myocardial ischemia-reperfusion injury / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which dripping pills (STDP) improves coronary microcirculation disorder (CMD) and cardiac dysfunction in a porcine model of myocardial ischemia-reperfusion injury.@*METHODS@#Fourteen minipigs were randomly selected for interventional balloon occlusion of the middle left anterior descending branch to induce CMD, and another 7 pigs received sham operation. The pig models of CMD were randomized equally into the model group and STDP-treated group. All the animals were fed with common feed for 8 weeks, and in STDP-treated group, the pigs were given STDP at the daily dose of 3 mg/kg (mixed with feed) for 8 weeks. Before and at the 8th week after the operation, the pigs underwent coronary angiography and echocardiography to determine the vessel lumen diameter and TIMI frame count (CTFC). The pathologies of the myocardium and the microvessels were examined with HE staining at the 8th week. Western blotting was used to detect the expression of silencing information regulator (Sirt1), peroxidase proliferator-activated receptor-γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), extracellular signal-regulated kinase1/2 (ERKI/2), Toll-like receptor 4 (TLR4), and uncoupling protein 2 (UCP2) in myocardial tissue.@*RESULTS@#Before and at the 8th week after the operation, the diameter of the anterior descending vessel in the 3 groups did not differ significantly ( > 0.05). At the 8th week, the number of CTFC frames in the model group increased significantly compared with that in the sham-operated group, but was obviously lowered by treatment with STDP ( < 0.05). Myocardial ischemia-reperfusion injury significantly increased the interventricular septal thickness at end-diastole, left ventricular end-diastole dimension, end-diastole volume, interventricular septal thickness at end-systole and left ventricular mass at 8 weeks after the modeling ( < 0.05), but such changes were significantly alleviated by treatment with STDP (P < 0.05). STDP treatment markedly alleviated myocardial microvascular congestion, thrombosis and peripheral inflammatory cell infiltration induced by myocardial ischemia-reperfusion, but atrophy of the myocardial muscle fiber remained distinct. STDP obviously suppressed the down-regulation of Sirt1, PGC-1α, and PPARα and the up-regulation of ERK1/ 2, TLR4, and UCP2 in the myocardial tissues induced by myocardial ischemia-reperfusion injury.@*CONCLUSIONS@#STDP has anti-inflammatory effects and regulates energy metabolism in the myocardium through modulating Sirt1, PGC-1α, PPARα, ERKI/2, TLR4, and UCP2 to improve CMD and cardiac dysfunction after myocardial ischemia-reperfusion.

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.

Correlation between CYP2C19 gene polymorphism and clinical efficacy of compound danshen dropping pills in treatment of senile coronary atherosclerotic heart disease / 中国中西医结合急救杂志

Objective To study the correlation between the polymorphism of CYP2C19 gene and the clinical efficacy of compound Danshen dripping pills in treatment of senile coronary atherosclerotic heart disease (CHD) and to provide theoretical basis for rational drug use. Methods Two hundred and six elderly patients with CHD treated in the Third Hospital of Hebei Medical University from June 2015 to December 2017 were screened for genotype detection and classification. All patients were given oral compound Danshen dripping pills, 10 pills each time, 3 times a day, for consecutive 2 months. Serological indexes, electrocardiograph (ECG) monitoring, liver and kidney function testing were performed before and after treatment to evaluate drug efficacy and adverse reactions. Results In senile patients with CHD, after taking compound danshen dripping pills for 2 months, the efficacy in patients with intermediate metabolizer (IM) was more significantly effective than the efficacies of the patients with extensive metabolizer (EM) and poor metabolizer (PM) [clinical efficacy: 95.6% (87/91) vs. 80.5% (33/41), 93.2% (69/74), ECG efficacy: 95.6% (87/91) vs. 78.0% (32/41), 94.6% (70/74)], at the same time, the serum levels of triglyceride (TG) and high-density lipoprotein (HDL) in patients with IM were also higher than those in patients with PM and EM [TG (mmol/L): 1.33±0.52 vs. 1.33±0.41, 1.33±0.27, HDL (mmol/L): 1.58±1.17 vs. 1.44±0.65, 1.38±0.18], and the levels of total cholesterol (TC), low-density lipoprotein (LDL) and hypersensitive C-reactive protein (hs-CRP) were lower than those of PM and EM [TC (mmol/L): 3.48±0.25 vs. 3.56±0.96, 3.51±0.51, LDL (mmol/L): 2.19±0.35 vs. 2.23±0.49, 2.21±0.87, hs-CRP (mg/L): 3.50±1.07 vs. 3.53±1.51, 3.54±2.01]. The incidences of adverse reactions in patients with EM and IM were significantly lower than the incidence of PM [6.8% (5/74), 9.9% (9/91) vs. 31.7% (13/41)], the differences being statistically significant (both P < 0.05). Conclusions CYP2C19 gene polymorphism is closely related to C HD in elderly, in such patients with IM, after taking compound Danshen dripping pills, the efficacy is significant and has low incidence of adverse reactions. Therefore, in the course of clinical treatment of elderly patients with CHD, genetic testing should be carried out to fully consider the influence of CYP2C19 gene polymorphism on the efficacy of the pill, and adopting personalized therapy can increase efficacy and reduce toxicity.

Quality control for Ganneng Dripping Pills based on quantitative analysis on multi-components with single marker / 中草药

Objective: To establish a quantitative analysis of multi-components by single mark (QAMS) for determining the content of eight components in Ganneng Dripping Pills (GDP) and its active pharmaceutical ingredients (APIs), including dehydrodiconiferyl alcohol, herpetotriol I, herpetolide A, herpetrione, herpetin, herpetetrone, herpetone, and herpetenone. Methods: Based on HPLC method, the relative correction factors (fk/m) were established with the herpetrione as the internal reference, and the content of other seven components was calculated. Moreover, the content of eight components in five batches of GDP and its APIs were determined by the external standard method (EMS), and the difference between the calculated value and the measured value were compared to verify the accuracy and feasibility of QAMS. Results: The fk/m value of dehydrodiconiferyl alcohol, herpetotriol I, herpetolide A, herpetin, herpetetrone, herpetone, and herpetenone with reference to herpetrione were 0.908, 0.728, 0.516, 0.720, 0.461, 0.623, and 0.410, respectively; And it had good reproducibility under different conditions. There were no significantly differences in the content of eight components between EMS and QAMS. Conclusion: Using GAPDH as an internal standard, the QAMS for determining the contents of eight components in GDP and raw material medicine was reliable and accurate and could be applied to control the quality of GDP.

Quality marker research of monarch herb Salvia miltiorrhiza in Compound Danshen Dripping Pills / 中草药

To explore the chemical ingredients of Salvia miltiorrhiza in Compound Danshen Dripping Pills (CDDP) based on the concept of quality marker (Q-marker). Methods The main salvianolic acids of S. miltiorrhiza and CDDP were determined by UPLC method. According to the extraction process of CDDP chemical transformation of salvianolic acids, including lithospermic acid, salvianolic acids B, E, U, and T were studied. Results Salvianolic acid B and rosmarinic acid, more than 90.0% and 5.0% of total salvianolic acid, were the main salvianolic acids in S. miltiorrhiza. But in CDDP, eight salvianolic acids (danshensu, protocatechuic aldehyde, salvianolic acids A, B, D, T, and U) were the main salvianolic acids. And the contents of danshensu and protocatechuic aldehyde were higher than the other six salvianolic acids. Through the study on chemical transformation of salvianolic acids, it was proved that lithospermic acid, salvianolic acids B, E, U, and T could transform into other salvianolic acids with smaller molecular weight, and danshensu and protocatechuic aldehyde were the main end products. Conclusion It is scientific to choose salvianolic acid B as the Q-marker of salvianolic acids of S. miltiorrhiza, and danshensu as the primary Q-marker. During the preparation of CDDP, salvianolic acids from S. miltiorrhiza have chemical chages, eight main salvianolic acids of which have been produced. The contens of danshensu and protocatechuic aldehyde are the highest in the eight salvianolic acids. From the chemical composition level, it is scientific and reasonable to choose danshensu as the Q-marker of monarch herb S. miltiorrhiza in CDDP.

Active ingredients screening by cell membrane chromatography and simultaneous quantitation of ginsenosides in bulk drug of secondary ginsenoside H dripping pills / 中草药

To establish a HPLC-MS/MS method for simultaneous determination and active ingredients screening of pseudoginsenoside RT5, 20(S)-ginsenoside Rh1 and 20(S)-ginsenoside Rh2 by cell membrane chromatography (CMC) in secondary ginsenoside H dripping pills (SGHDP). Methods The samples were separated on Century SIL BDS C18 column (250 mm × 4.6 mm, 5 μm) eluted with 0.2% formic acid aqueous solution-acetonitrile in a gradient mode, and the target compounds were analyzed by positive ion multiple reaction monitoring (MRM) mode, and active ingredients of SGHDP obtained in solid-phase of biomembrane by CMC technology were determined at the same time. Results The linear ranges of pseudoginsenoside RT5, 20(S)-ginsenoside Rh1, and 20(S)-ginsenoside Rh2 were 0.095-0.235, 0.042-0.168, and 0.105-0.419 mg/mL; the extraction recoveries were 99.95%, 100.12%, and 100.06%; and RSD were 1.06%, 0.96%, and 0.91%, respectively. The contents of pseudoginsenoside RT5, 20(S)-ginsenoside Rh1, and 20(S)-ginsenoside Rh2 in SGHDP were 21.24%, 21.42%, and 29.70%, respectively. 20(S)-Ginsenoside Rh2 was the active ingredient obtained by biomembrane using as a new quality control maker for SGHDP. Conclusion The developed method is accurate and reliable for the determination of three ginsenosides in SGHDP, and provides a new reference for quality control of SGHDP. 20(S)-Ginsenoside Rh2 is a immobilization component of red cell membrane, speculated to be the active ingredient of SGHDP, which is in consistent with previous studies on antitumor and antidepression.

Metabolomics Research on Compound Danshen DrippingPills in Acute Myocardial Infarction Rat / 分析化学

An acute myocardial infarction rat model was established by ligation of the left ventricular coronary artery.Plasma samples of rats were collected and analyzed by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to study the myocardial protection mechanism of compound Danshen dropping pill (CDDP).After principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), 22 metabolites were identified as potential biomarker of AMI.Furthermore, CDDP had remarkable effect on AMI rats.p-Tolyl sulfate, hippuric acid, equol 7-O-glucuronide, lysoPC(16∶0), cholic acid, oleamide, palmitic amide and SM(d18∶1/16∶0) were significantly changed in treatment group.The results showed that CDDP had a very good myocardial protection effect on AMI rats, and might influence the pathways of phenylalanine metabolism, glycerophospholipid metabolism, fatty acid metabolism, primary bile acid biosynthesis and Sphingolipid metabolism.

Research progress in fingerprint of Compound Danshen Dripping Pills and its raw materials / 药物评价研究

Compound Danshen Dripping Pills has curative effect of angina pectoris,coronary heart disease,and other cardiovascular and cerebrovascular diseases,which is widely used in clinic.With the development of basic research and clinical pharmacology,it is particularly important to carry out more comprehensive and systematic quality control.At present,fingerprint technology is developing rapidly and has been recognized by many countries.In this article,we summarized the research situation of Compound Danshen Dropping Pills and its raw materials from two aspects of chromatography and spectroscopy (such as LC,CE,IR,NMR and so on).It will provide reference or the further establishment of a reasonable quality control method.

Study on Quality Standard of Oleanolic Acid Dripping Pills / 中国药房

OBJECTIVE:To establish the quality standard of Oleanolic acid dripping pills. METHODS:The property of the preparation was identified,and weight difference and dissolution time limit were detected. UPLC method was adopted to determine the content of oleanolic acid in the preparation. The determination was performed on ACQUITY UPLC BEH C18 column with mo-bile phase consisted of acetonitrile-water (70:30,V/V) at the flow rate of 0.30 mL/min. The detection wavelength was set at 206 nm,the column temperature was 30 ℃,and the sample was 5 μL. RESULTS:The characteristics of the preparation was significant;weight difference ranged 37.62%-46.56%;dissolution time limit was 24 min. Linear range of oleanolic acid ranged 0.006-0.06 mg/mL (r=0.9998). RSDs of precision,stability and reproducibility tests were all lower than 2.0%. The recoveries were 99.34%-100.40%(RSD=0.4%,n=6). CONCLUSIONS:Established standard can be used for quality control of Oleanolic acid dripping pills.

Clinical Observation of Rosuvastatin Calcium Tablets Combined with Qishen Yiqi Dripping Pills in the Treatment of Chronic Heart Failure / 中国药房

OBJECTIVE:To investigate clinical efficacy and safety of Rosuvastatin calcium tablets combined with Qishen yiqi dripping pills in the treatment of chronic heart failure (CHF) and it effects on inflammatory level,oxidative stress injury and cardiac function of patients.METHODS:Ninety CHF patients in our hospital during Aug.2014-Apr.2016 were divided into observation group and control group according to random number table,with 45 cases in each group.Control group received routine anti-heart failure treatment as cardiac,diuretic,dilating vessel,and Qishen yiqi dripping pills orally 0.5 g,half an hour after meal,tid;observation group was additionally given Rosuvastatin calcium tablet orally 20 mg,at bedtime,qd,on the basis of control group.Cardiac function,serum inflammatory factor,BNP and oxidative stress levels were compared between 2 groups before and after treatment.Clinical efficacies and the occurrence of ADR were observed in 2 groups.RESULTS:Before treatment,there was no statistical significance in LVEF,LVESD,LVEDD,TNF-α,IL-6,BNP,SOD,MPO and MMP-9 levels between 2 groups (P＞0.05).After treatment,LVEF of 2 groups were increased significantly,while LVEDD,LVESD,TNF-α and IL-6,BNP levels were decreased significantly;the above indexes of observation group was significantly better than those of control group,with statistical significance (P＜0.05).MPO and MMP-9 of observation group were significantly decreased,while SOD level was significantly increased and better than that of control group,with statistical significance (P＜0.05),but there was no statistical significance in SOD and MPO,MMP-9 levels of control group before and after treatment (P＞0.05).The clinical response rate of observation group was 97.8％,which was significantly higher than 82.2％ of control group,with statistical significance (P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Rosuvastatin calcium tablets combined with Qishen yiqi dripping pills show significant therapeutic efficacy for CHF,can effectively reduce inflammatory level,relieve oxidant stress injury,delay the process of ventricular remodeling,and improve cardiac function with good safety.