Use of Qishen granule for the treatment of heart failure: A systematic review and meta-analysis of animal studies

Objective:To evaluate the effect of Qishen granule(QSG)on heart failure(HF)and the potential mechanisms involved in animal models.Methods:Studies of QSG in animals with HF were identified by searches of eight databases up to August 1,2019.Two authors independently reviewed each study and the Collaborative Approach to Metaanalysis and Review of Animal Data from Experimental Studies 10-item checklist was used for quality assessment.The primary outcomes were indicators of left ventricular ejection fraction and/or left ventricular fractional shortening.The secondary outcome measures were ventricular structure,hemodynamics,myocardial injury-related indicators,and the mechanisms whereby QSG ameliorates HF.A metaanalysis was performed and all the data were analyzed using RevMan 5.3 software.Results:Thirteen studies containing a total of 240 animals met the criteria for the meta-analysis.The quality score of the studies ranged from three to six points.The meta-analysis showed a significant effect of QSG to improve cardiac function,inhibit ventricular remodeling,improve circulation,and attenuate myocardial injury.The possible mechanisms was identified to be suppression of the renin-angiotensinaldosterone system,which has anti-fibrotic,anti-apoptotic,anti-inflammatory,and anti-oxidative effects in the myocardium,the prevention of calcium overload,and the promotion of myocardial energy metabolism.Conclusion:Our review shows that QSG has a cardioprotective effect in animal models of CHF.However,due to the relatively poor quality of the included studies and the differences between humans and animal models,the results should be interpreted with caution.

Cardioprotective Effects of Qishen Granule(芪参颗粒)on Sarcoplasmic Reticulum Ca^2＋ Handling in Heart Failure Rats

Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham（n=10）, model（n=10）, QSG（n=12, 2.2 g/kg daily） and metoprolol groups（n=12, 10.5 mg/kg daily）. The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results：HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.

Qishen Taohong Granule as Adjuvant Therapy for Improving Cardiac Function and Quality of Life in Patients with Chronic Heart Failure:A Randomized Controlled Trial

Objective:To confirm the improvement of cardiac function and quality of life(QoL)in patients with chronic heart failure(CHF)via Chinese medicine(CM)Qishen Taohong Granule(QTG).Methods:This study was a single-center,prospective,randomized,controlled clinical trial.Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association(NYHA)classⅡorⅢin stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine(TMZ),in addition to their standard medications for the treatment of CHF.The study period was 4 weeks.The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction(LVEF),as well as QoL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale(CHFQLS).The secondary outcomes included 6-min walking test(6 MWT),CM syndrome score,symptom and sign scores and N-terminal pro-B-type natriuretic peptide level(NT-proBNP).All indices were measured at baseline and the end of the trial.Results:At the 4-week follow-up period,the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group(74.29%vs.54.29%,P<0.05).But there was no significant difference in posttreatment level of LVEF between the two groups(P>0.05).The CHFQLS scores improved by 13.82±6.04 vs.7.49±2.28 in the QTG and TMZ groups,respectively(P<0.05).Subgroup analysis of the CHFQLS results showed that physiological function,role limitation and vitality were significantly higher in the QTG group than in the TMZ group(15.76±7.85 vs.7.40±3.36,P<0.05;16.00±8.35 vs.10.53±4.64,P<0.05;15.31±8.09 vs.7.89±4.60,P<0.05).Compared with TMZ group,treatment with QTG also demonstrated superior performance with respect to 6 MWT,CM syndrome,shortness of breath,fatigue,gasping,general edema and NT-proBNP level.No significant adverse reactions or adverse cardiac events occurred during treatment in either group.Conclusion:In addition to conventional treatments,the use of QTG as an adjuvant therapy significantly improved cardiac function and QoL in patients with CHF classⅡorⅢin stage C.[Registration No.ChiCTR1900022036(retrospectively registered)]