Effect of Qishen Yiqi dripping pills combined with trimetazidine on the treatment of chronic heart failure: A meta-analysis

Objective:To systematically evaluate the safety and effectiveness of Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure.Methods:A total of four English and Chinese electronic databases were searched:CNKI,VIP,CBM,PUBMED.Cochrane bias risk tools were used to assess the methodological quality of qualified studies.Meta-analysis was conducted by Review Manager 5.3.A total of 9 articles were included,with a total sample size of 855 cases,443 cases in the observation group and 412 cases in the treatment group.Results:Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure has a total effective rate(RR=1.22,95%CI[1.15-1.30];p<0.00001),LVEF(MD=6.03,95%CI[5.39,6.67],P<0.00001),BNP(MD=-101.87,95%CI[-109.90,-93.83],P<0.00001),E/A(MD=-4.32,95%CI[-5.70,-2.93],P<0.00001),SYP(MD=-10.32,95%CI[-13.32,-7.32],P<0.00001),LVESD(MD=-5.50,95%CI[-6.03,-4.96],P<0.00001),6-MWT(MD=110.13,95%CI[96.89,123.36],P<0.00001)Adverse reactions occurred less frequently and did not affect treatment.Conclusion:This study shows that QYDP combined with TMZ can improve various indicators of CHF patients.However,due to the small sample size and the generally low quality of research,a more rigorous and reasonably designed RCT is needed to confirm these findings.

Integrated UHPLC-MS and network pharmacology to explore the active constituents and pharmacological mechanisms of Shenzao dripping pills against coronary heart disease

Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.

Clinical Intervention Effect of Compound Danshen Dripping Pills on Aspirin Resistant Patients with Coronary Heart Disease

[Objectives]To study the clinical intervention effect of Compound Danshen Dripping Pills on aspirin-resistant patients with coronary heart disease(CHD).[Methods]240 patients with coronary heart disease who took Aspirin were selected to measure thrombocytopenia by sonoclot.They were randomly divided into four groups:group A(n=60),Compound Danshen Dripping Pills and aspirin.group B(n=60),aspirin;group C(n=60),high dose aspirin;group D(n=60),Compound Danshen Dripping Pills.CR and PF were determined by sonoclot after one month.The incidence of angina pectoris,acute myocardial infarction,sudden cardiac death and hemorrhage were observed.[Results]After treatment,the CR and PF levels of group A and C were significantly lower than those before treatment,and there was no significant difference between group B and D and before treatment.After treatment,the levels of CR and PF in group A and C were significantly lower than those in group B and D,and there was a significant difference.Angina pectoris and myocardial infarction events in group D were significantly higher than the other four groups;hemorrhage events in group C were significantly higher than the other three groups.[Conclusions]Compound Danshen Dripping Pills combined with aspirin can be used as an economical,effective,and more dependent alternative to inhibit platelet activity in aspirin resistance,and can further reduce the occurrence of acute coronary events.

Effects of compound danshen dripping pills on the levels of serum inflammatory factors, brain natriuretic peptide and blood lipid in CABG postoperative patients

Objective:To explore the effects of compound danshen dripping pills on the levels of serum inflammatory factors,brain natriuretic peptide(BNP)and blood lipid in CABG postoperative patients.Methods:156 cases of patients who were given CABG from January 2015 to January 2018 in Baogang Hospital were chosen and randomly divided into the observation group(n=78)and the control group(n=78).Both groups were given conventional drugs,simultaneously,the observation group was given compound danshen dripping pills.The treatment lasted 3 months.The clinical efficacy was compared between two groups of patients,and the levels of serum inflammatory factors,plasma BNP and blood lipid before and after treatment in two groups of patients were detected in order to make a comparison in the incidence of adverse cardiac events between two groups of patients.Results:After treatment,the total effective rate of treatment in the observation group was significantly higher than that in the control group;in the two groups,the levels of serum interleukin-6(IL-6),interleukin-8(IL-8),C-reactive protein and plasma BNP after treatment were obviously lower than those before treatment,and these indicators in the observation group were lower than those in the control group(p<.05);the levels of TG,TC and LDL-C in two groups were obviously lower(p<.05)with the level of HDL-C significantly higher(all p<.05),and the descending or ascending range of each indicator in the observation group was obviously larger than that in the control group(p<.05);in the follow-up visit,the incidence of adverse cardiac events in the observation group of patients was significantly lower than that in the control group of patients(p<.05).Conclusions:Compound danshen dripping pills can effectively reduce the levels of serum inflammatory factors and BNP,regulate blood lipid metabolism and reduce the incidence of adverse cardiac events in CABG postoperative patients.

Effect of Guanxin Danshen Dripping Pills on Coronary Heart Disease Comorbid with Depression or Anxiety: The ADECODE-Real World Study

Objective: To evaluate the efficacy of Guanxin Danshen Dripping Pill(GXDSDP) in treating anxiety and depression in patients with coronary heart disease(CHD). Methods: A total of 1,428 patients diagnosed with CHD screened for anxiety, depression, and quality of life(QOL) at baseline received 0.4 g of GXDSDP treatment 3 times per day and returned for monthly reassessment. Patients were recruited after stable treatment for CHD and received assessment of General Anxiety Disorder-7(GAD-7), Patient Health Questionnaire-9(PHQ-9), and Seattle Angina Questionnaire(SAQ) for evaluating anxiety, depression, and QOL.Patients were followed up 3 times, once every 4 weeks, during outpatient visits for 12 weeks. Results: At the third follow-up(F3), the anxiety symptom of 63.79%(673/1,055) of the patients improved to sub-clinical level, and the GAD-7 score improved significantly(8.11 vs. 3.87, P<0.01);57.52%(585/1,017) patients' depressive symptoms improved to sub-clinical level, with a significant improvement in PHQ-9 score(8.69 vs. 4.41, P<0.01) at F3. All aspects of QOL significantly improved at the end of treatment compared to those at baseline(all P<0.01) as assessed by SAQ: physical limitation(31.17 vs. 34.14), anginal stability(2.74 vs. 4.14), anginal frequency(8.16vs. 9.10), treatment satisfaction(13.43 vs. 16.29), and disease perception(8.69 vs. 11.02). Conclusions: A fixed dosage of GXDSDP may be a potential treatment option for CHD patients comorbid with anxiety or depression.(Registration No. ChiCTR2100051523)

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

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,doubleblind,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

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.

Liqi Huoxue dripping pill protects against myocardial ischemia-reperfusion injury via the PI3K/Akt/GSK-3β signaling pathway in rats

Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway.

Anti-asthmatic mechanism of the Huashanshen dripping pill via suppressing contraction of the airway smooth muscle

Background:The Huashanshen(HSS)dripping pill has been widely used in asthma for a long time in China.However,the relaxant mechanism of HSS is not well understood.Methods:In this report,high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify the constituents in rat plasma after oral administration of HSS.Ovalbumin-sensitized allergic asthma and isolated trachea were studied for the anti-asthmatic mechanism of HSS.Results:D-anisodamine,L-anisodamine,scopolamine and atropine were detected in the rat plasma containing HSS.It was clear that the HSS inhibited the release of inflammatory mediators,regulated the balance of T-helper 1 and T-helper 2 to reduce the airway inflammation,and relaxed the tracheal smooth muscle by controlling the KCa channel,Ca^(2+)influx and release to reduce the airway hyperresponsiveness.Conclusion:Atropine,anisodamine and scopolamine might be active compounds of HSS which inhibited the release of inflammatory mediators,regulated the balance of Th1/Th2,and relaxed the tracheal smooth muscle to reduce airway hyperresponsiveness.

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.

Systematic review and Meta-analysis of 26 randomized controlled clinical trials of Compound Danshen Dripping Pill for non-proliferating diabetic retinopathy

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 Pub Med,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,Metaregression,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 Metaregression 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 Sijunzi Dripping Pill on Gastrointestinal Motility of Mice

Objective To study the effects of Sijunzi Dripping Pill（SDP）on gastrointestinal motilityof mice.Methods The diarrhea and swimming model of mice was made by Rhei Radixet Rhizoma-induced spleen deficiency.The intestinal transit,gastric emptying test,serum motilin（MTL）,vasoactive intestinal peptide（VIP）,and substance P（SP）were chosen to observe the effects of high-,mid-,and low-dose SDP on stomach movements,and the water extractive of Sijunzi Decoction was used as positive control.Results Compared with the control group,the gastric emptying rate in the gastrointestinal motility group was significantly decreased,the intestinal propulsion rate was obviously increased,the levels of MTL,prostaglandin E2（PGE2）,and SP were increased（P〈0.05）,while the level of VIP was decreased（P〈0.05）.Compared with the model group,SDP could decrease the intestinal transit rate,whereas increase the gastric emptying rate and the level of MTL（P〈0.05）;The high-dose SDP could decrease the level of PGE2（P〈0.05）and the low-dose SDP could decrease the level of VIP（P〈0.05）;Each group had no significant effect on SP.Conclusion SDP has the good effect on increasing the gastrointestinal motility of mice,and its function may partly relate to the regulation of the levels of MTL and VIP as well as PGE2.