Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial

Objective:To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction(HFpEF).Methods:Sixty patients with HFpEF were randomly divided into group A(n=20),receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks;group B(n=20),receiving conventional drugs combined with home-based exercise training for 12 weeks;and group C(n=20),receiving conventional drug treatment only.Peak oxygen uptake(peakVO2),anaerobic threshold(AT),6-min walking test(6MWT),Pittsburgh Sleep Quality Index(PSQI),and SF-36 questionnaire(SF-36)results before and after treatment were compared among groups.Results:After the 12-week intervention,patients in group C showed significant declines in peakVO2,AT,6MWT,PSQI,and SF-36 compared with pre-treatment(P<0.01),while groups A and B both showed significant improvements in peakVO2,AT,6MWT,PSQI,and SF-36 results compared with pre-treatment(P<0.01).Compared with group C,patients in groups A and B showed significant improvements in peakVO2,AT,6MWT,PSQI,and SF-36(P<0.01).In addition,patients in group A showed more significant improvements in physical function,role-physical,vitality,and mental health scores on the SF-36 questionnaire,and PSQI scores than those in group B(P<0.01).Conclusions:Exercise training improved exercise tolerance,sleep quality and quality of life(QoL)in patients with HFpEF.Notably,Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF.

Effectiveness and safety of Shexiang Baoxin Pill(MUSKARDIA)in patients with stable coronary artery disease and concomitant diabetes mellitus:a subgroup analysis of a randomized clinical trial

Background:Preliminary studies have indicated that Shexiang Baoxin Pill(MUSKARDIA)has a coronary artery dilation effect and increases the coronary blood flow,relieving the symptoms of angina.This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease(CAD)and diabetes mellitus(DM).Methods:This was a subgroup analysis of a multicenter,randomized,placebo-controlled phase IV trial.CAD patients with a medical history of DM or baseline fasting blood glucose(FBG)≥7.0 mmol/L were grouped according to the treatment(standard therapy plus MUSKARDIA or placebo).The primary outcome was major adverse cardiovascular events(MACEs),which was the composite outcome of cardiovascular death,non-fatal myocardial infarction,and non-fatal stroke.The secondary outcome was the composite outcome of all-cause death,non-fatal myocardial infarction,non-fatal stroke,hospitalization for unstable angina or heart failure,and coronary angioplasty.Results:MACEs occurred in 2.6%(9/340)and 4.8%(18/376)of patients in the MUSKARDIA and placebo groups,respectively(P=0.192).Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo(15.3%[52/340]vs.22.6%[85/376],P=0.017).Risk of MACEs(hazard ratio[HR]=0.69,95%confidence interval[CI]:0.31-1.57)was comparable between two groups.In patients with uncontrolled DM(≥4 measurements of FBG≥7 mmol/L in five times of follow-up),the risk of secondary outcome was significantly lower with MUSKARDIA(5/83,6.0%)than with placebo(15/91,16.5%)(HR=0.35,95%CI:0.13-0.95).Conclusion:As an add-on to standard therapy,MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM.Furthermore,MUSKARDIA may reduce the frequency of all-cause death,hospitalization,and coronary angioplasty in this population,especially in those with uncontrolled DM.Trial Registration:ChiCTR.org.cn,ChiCTR-TRC-12003513.

Shexiang Baoxin Pill Regulates Intimal Hyperplasia,Migration,and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451

Objective:To investigate the regulatory roles of Shexiang Baoxin Pill(SXBXW)in neointimal formation and vascular smooth muscle cells(VSMCs)invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury(platelet-derived growth factor(PDGF)-BBstimulated)in vitro.Methods:VSMCs were randomly assigned to 5 groups:blank,PDGF-BB(20 ng/mL+0.1%DMSO),SXBXW-L(PDGF-BB 20 ng/mL+SXBXW low dose 0.625 g/L),SXBXW-M(PDGF-BB 20 ng/mL+SXBXW medium dose 1.25 g/L)and SXBXW-H(PDGF-BB 20 ng/mL+SXBXW high dose 2.5 g/L)group.Cell proliferation was assessed using cell counting kit-8(CCK-8)assay and bromodeoxyuridine(BrdU)incorporation assay,the migration effects were detected by Transwell assay,cell apoptosis rate was measured by the Annexin V/propidium iodide(PI)apoptosis kit.The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining.To validate the effects of miR-451 in regulating proliferation,migration and apoptosis treated with SXBXW,miR-451 overexpression experiments were performed,the VSMCs were exposed to PDGF-BB 20 ng/mL+0.1%DMSO and later divided into 4 groups:mimic-NC(multiplicity of infection,MOI=50),SXBXW(1.25 g/L)+mimic-NC,mimic-miR451(MOI=50),and SXBXW(1.25 g/L)+mimic-miR451,and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.Results:PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration.SXBXW inhibited phenotypic switching,proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs.In addition,miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation.SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs(P<0.05).Compared with SXBXW+mimic-NC and mimicmiR451 groups,the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta(Ywhaz)and p53 was further reduced in SXBXW+mimic-miR451 group,while activating transcription factor 2(ATF2)was increased in VSMCs(P<0.05).Conclusion:SXBXW regulated proliferation,migration and apoptosis via activation of miR-451 through ATF2,p53 and Ywhaz in PDGF-BB-stimulated VSMCs.

Effect of Shexiang Baoxin Pill(麝香保心丸) in Alleviating Early Hypertensive Renal Injury in Rats

Objective:To investigate the effect of Shexiang Baoxin Pill(麝香保心丸,SBP)on early hypertensive renal injury in rats and to explore the possible mechanism.Methods:Twelve-week-old spontaneous hypertensive rats(SHRs)with high-salt diet(dietary containing 8%NaCl)were randomized into the SBP group[40 mg/(kg·d)],losartan potassium group[20 mg/(kg·d)]and saline group by stratified random sampling method,12 in each group.Blood pressure and urea albumin creatinine ratio were measured.After 10 weeks,the expression levels of serum creatinine(Scr),hypersensitive C-reactive protein(hs-CRP),interleukin(IL)-1β,IL-6,tumor necrosis factorα(TNF-α),and transforming growth factorβ(TGF-β)in serum were assessed.Kidney pathology periodate-schiff staining was performed.Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining.Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4(TLR4),nuclear factorκB(NF-κB),monocyte chemokine peptide(MCP-1),inducible nitric oxide synthase(iNOS),and arginase-1(Arg-1).Results:SBP did not affect the mortality of SHR(P<0.05).SBP significantly reduced the level of elevated blood pressure of SHRs,but the effect was less significantly than that of losartan potassium.SBP decreased urine protein(P<0.01)and the expression levels of IL-1β,IL-6,TNF-α,and TGF-βin serum.The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells,glomerular ischemic lesions,inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis.Both SBP and losartan potassium had alleviated renal pathological change,and significantly reduced the infiltration of macrophage(P<0.05,P<0.01).SBP and losartan potassium decreased the expressions of TLR4,NF-κB,MCP-1,iNOS,and Arg-1.Conclusion:SBP significantly modified the early hypertensive renal injury by reducing inflammation,and the effect was similar to losartan potassium.

Exploring the Pathways and Targets of Shexiang Baoxin Pill for Coronary Heart Disease through a Network Pharmacology Approach

Objective: To investigate the network pharmacology of Shexiang Baoxin pill(SBP) and systematically analyze the mechanisms of SBP.Methods: In this study, we excavated all the targets of 26 constituents of SBP which were identified in rat plasma though literature mining and target calculation(reverse docking and similarity search) and analyzed the multiple pharmacology actions of SBP comprehensively through a network pharmacology approach.Results: In the end, a total of 330 Homo sapiens targets were identified for 26 blood constituents of SBP.Moreover, the pathway enrichment analysis found that these targets mapped into 171 KEGG pathways and 31 of which were more enriched.Among these identified pathways, 3 pathways were selected for analyzing the mechanisms of SBP for treating coronary heart disease.Conclusion: This study systematically illustrated the mechanisms of the SBP by analyzing the corresponding "drug-target-pathway-disease" interaction network.

Assessment of Effect of Shexiang Baoxin Pill for Labour Angina Pectoris Patients with Computerized Tomography Myocardial Imaging

Objective:To assess the effect of Shexiang Baoxin Pill（SXBXP）for labour angina pectoris.Methods:Effect of 66 patientstreated withconven tional treatment or conventional treatment plus SXBXP were observed and compared with^(99m) TC-MIBI singlepho tonemissi on computerized tomography（SPECT）target cardiograph to estimate is chemia my ocardial area.Results:The total effectiverate was much higher in patients treated with SXBXP than that in patients treated with conventional treatment only（87.8%vs.56%,P＜0.05）.The effective rate on ECG in the two group swas 70.7% and 52%respectively,with out significant statistical difference between them（P＞0.05）.While significant difference was observed in is chemiaarea of my ocardiali mage between the two groups after treatment,18.2±8.2%vs23.8±9.8%,P<0.05.Moreover,there currence of anginapect or is and cardiaceven twerealsolessin the SXBXPgroup.Conclusion:the SXBXP was effective for labourangina pectoris.