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Shexiang Baoxin Pill for Acute Myocardial Infarction: Clinical Evidence and Molecular Mechanism of Antioxidative Stress.

ABSTRACT: Acute myocardial infarction (AMI) has been a preclinical and clinical concern due to high hospitalization rate and mortality. This study was aimed at evaluating the effectiveness and safety of Shexiang Baoxin Pill (SBP) for AMI and exploring the possible mechanism of oxidative stress. Six databases were searched on March 26, 2021. Twenty-four studies were included and accessed by the RoB 2.0 or SYRCLE tool. Compared with routine treatment (RT), SBP showed the effectiveness in the clinical efficacy (RR = 1.15, 95% CI [1.06, 1.25]), left ventricular ejection fraction (LVEF) (SMD = 0.73, 95% CI [0.62, 0.95]), glutathione (GSH) (SMD = 2.07, 95% CI [1.51, 2.64]), superoxide dismutase (SOD) (SMD = 0.92, 95% CI [0.58, 1.26]), malondialdehyde (MDA) (SMD = -4.23, 95% CI [-5.80, -2.66]), creatine kinase-myocardial band (CK-MB) (SMD = -4.98, 95% CI [-5.64, -4.33]), cardiac troponin I (cTnI) (SMD = -2.17, 95% CI [-2.57, -1.76]), high-sensitivity C-reactive protein (Hs-CRP) (SMD = -1.34, 95% CI [-1.56, -1.12]), interleukin-6 (IL-6) (SMD = -0.99, 95% CI [-1.26, -0.71]), triglycerides (TG) (SMD = -0.52, 95% CI [-0.83, -0.22]), flow-mediated dilation (FMD) (SMD = 1.39, 95% CI [1.06, 1.72]), von Willebrand Factor (vWF) (SMD = -1.77, 95% CI [-2.39, -1.15]), nitric oxide (NO) (SMD = 0.89, 95% CI [0.65, 1.13]), and recurrent rate (RR = 0.30, 95% CI [0.15, 0.59]). But SBP adjunctive to RT plus PCI had no improvements in almost pooled outcomes except for the Hs-CRP (SMD = -1.19, 95% CI [-1.44, -0.94]) and TG (SMD = -0.25, 95% CI [-0.48, -0.02]). Laboratory findings showed that SBP enhanced the endothelial nitric oxide synthase (eNOS) activity and regulated laboratory indexes especially for homocysteine. In conclusion, SBP has adjunctive effects on AMI via the mechanism of antioxidative stress. The current evidence supports the use of SBP for mild and moderate AMI patients.

SUBMITTER: Guo J

PROVIDER: S-EPMC8652282 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ethnopharmacological relevance: Shexiang Baoxin Pill (SBP) is a traditional formulation of a Chinese patent medicine, which has been commonly used for the treatment of cardiovascular disease (CVD) in China since the 1980s. Previous clinical studies have shown that SBP is safe and effective in patients with CVD, but the mechanism of the therapeutic effect is still poorly understood and requires further research. Aim of the study: This study aims to comprehensively understand the effects and the underlying mechanisms of SBP for CVD treatment by analyzing the whole proteome of myocardial infarction (MI) model rats with or without SBP treatment. Materials and methods: We evaluated the therapeutic effects of SBP on myocardial infarction model (MI) rats by performing the echocardiography analyses after 15-day treatment. And the label-free quantitative proteomic approach was utilized to investigate the whole proteome of the rat heart tissues from MI group (MI rats, n=3), SBP group (MI rats treated with SBP, n=3) and SOG group (sham operated rats, n=3) on the operation day (Day 0) and 15 days after operation (Day 15), respectively. The differentially expressed proteins were subsequently analyzed with bioinformatical methods such as KEGG pathway enrichment analysis, gene ontology (GO)-annotation analysis and protein-protein interaction (PPI) network analysis. Finally, the expression levels of two promising proteins were validated by immunoblotting. Results: The echocardiography analyses show SBP significantly improved the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) of MI rats. Additionally, 134 proteins were differentially expressed both between SBP/MI and SOG/MI, and 15 proteins were found closely related to CVD. The pathway enrichment and GO-annotation analysis of these differentially expressed proteins revealed that the proteins involved in cellular mitochondrial energy metabolism processes, such as fatty acid beta-oxidation and aerobic respiration, were significantly regulated under SBP treatments, of which fatty acid-binding protein 3 (FABP3) and myoglobin (MB) was significantly down-regulated in MI model group compared with SOG group and was returned to the basal level by SBP treatment. Expression levels of these two proteins were confirmed by immunoblotting experiments. Conclusions: These results we obtained in current study probably demonstrated that the cardio-protective effects of Shexiang Baoxin Pill might be achieved through the regulation of energy metabolism homeostasis in cardiac tissue.

Project description:Background: The coronary microvascular dysfunction has attracted more and more attention in recent years, but there is still a lack of effective treatment. Shexiang Baoxin Pill is one of the commonly used drugs for the treatment of coronary artery disease in China. More recently, some studies found that it has the effect of improving coronary microvascular function. Objective: To evaluate the effects of Shexiang Baoxin Pill for coronary microvascular function. Methods: Databases including MEDLINE, Web of Science, CNKI, Wanfang, The Cochrane Library, EMbase, VIP and CBM were searched from inception to June 2021 to screen out relevant clinical studies. The 2019 version 2 of the Cochrane risk of bias tool (RoB2) were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. Results: Eleven studies meeting the criteria were included, with a total of 1,075 patients. The results of meta-analysis showed that compared with conventional treatment alone, combination of Shexiang Baoxin Pill and conventional treatment can further increase the coronary flow reserve (CFR) [mean difference (MD) = 0.43, 95%CI (0.28, 0.58), p < 0.000 01], decrease the index of microvascular resistance (IMR) [MD = -4.23, 95%CI (-5.49, -2.97), p < 0.000 01], increase serum nitric oxide (NO) [MD = 11.96, 95%CI (2.74, 21.18), p = 0.001] and decrease serum hypersensitive C-reactive protein (hs-CRP) [MD = -2.49, 95%CI (-3.08, -1.90), p < 0.000 01], but did not increase the time of duration on the exercise testing (TET) [MD = 3.64, 95%CI (-1.17, 8.45), p = 0.14]. In terms of safety, a total of 10 patients developed adverse reactions in the intervention group and 17 patients developed adverse reactions in the control group. Conclusion: Current evidence suggests that Shexiang Baoxin Pill may be effective in the improvement of coronary microvascular function when used in combination with conventional treatment. However, due to the low quality of the included studies, lack of placebo control and high heterogeneity among different studies, we should take a cautious attitude towards this conclusion. Moreover, the safety of Shexiang Baoxin Pill remains uncertain, more high-quality clinical studies are needed to verify the efficacy and safety of this drug in the future. Systematic Review Registration: [website], identifier [registration number: CRD42021265113].

Project description:Aim: The Shexiang Baoxin Pill (SBP) has been extensively used to treat cardiovascular diseases in China for four decades, and its clinical efficacy has been widely approved. However, the mechanism by which this is achieved remains largely unexplored. Research attempting to understand the underlying mechanism is ongoing, but the findings are controversial. Here, we aimed to explore the possible mechanism of SBP in myocardial ischemia-reperfusion (I/R) injury using heart single-nucleus and spatial ribonucleic acid (RNA) sequencing. Methods: We established a murine myocardial I/R injury model in C57BL/6 mice by ligating and recanalizing the left coronary artery anterior descending branch. Subsequently, single-nucleus RNA-seq and spatial transcriptomics were performed on mice cardiac tissue. We initially assessed the status of cell types and subsets in the model administered with or without SBP. Results: We used single-nucleus RNA sequencing to comprehensively analyze cell types in the cardiac tissue of sham, I/R, and SBP mice. Nine samples from nine individuals were analyzed, and 75,546 cells were obtained. We classified the cells into 28 clusters based on their expression characteristics and annotated them into seven cell types: cardiomyocytes, endothelial cells, fibroblasts, myeloid cells, smooth muscle cells, B cells, and T cells. The SBP group had distinct cellular compositions and features than the I/R group. Furthermore, SBP-induced cardioprotection against I/R was associated with enhanced cardiac contractility, reduced endocardial cell injury, increased endocardial-mediated angiogenesis, and inhibited fibroblast proliferation. In addition, macrophages had active properties. Conclusion: SBP improves the early LVEF of I/R mice and has a cardioprotective effect. Through sequencing analysis, we observed that SBP can increase the gene expression of Nppb and Npr3 in the infarct area of the heart. Npr3 is related to vascular generation mediated by endocardial cells and requires further research. In addition, SBP increases the number of fibroblasts, inhibits the expression of genes related to fibroblast activation and proliferation, and increases the transformation of endothelial cells into fibroblasts. These findings will help to indicate directions for further research.

Project description:BackgroundRecent evidence indicates that Shexiang Baoxin Pill (MUSKARDIA), as an add-on treatment to standard therapy for stable coronary artery disease (CAD), is effective. Nevertheless, the cost-effectiveness of introducing the Shexiang Baoxin Pill (Abbreviation SBP) to the current standard treatment for patients with CAD in China remains unknown.ObjectiveThe objective of this study was to assess the cost-effectiveness of introducing SBP into the current standard treatment in China for patients with CAD.MethodThe effects of two treatment strategies-the SBP group (SBP combined with standard therapy) and the standard therapy group (placebo combined with standard therapy)-were simulated using a long-term Markov model. The simulation subjects might experience non-fatal MI and/or stroke or vascular or non-vascular death events. The study parameters were primarily derived from the MUSKARDIA trial, which was a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial. Furthermore, age-related change, event costs, and event utilities were drawn from publicly available sources. Both costs and health outcomes were discounted at 5.0% per annum. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. Based on the MUSKARDIA trial results, the risk with the events of major adverse cardiovascular events (MACE) was decreased (P < 0.05) in the female subgroup treated with SBP therapy compared with standard therapy. Consequently, a scenario analysis based on subgroups of Chinese females was conducted for this study. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per quality-adjusted life-year (QALY) saved.ResultsAfter 30 years of simulation, the SBP group has added 0.32 QALYs, and the cost has been saved 841.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -2628.13 CNY per QALY. Scenario analyses of Chinese females showed that, after 30 years of simulation, the SBP therapy has been increased by 0.82 QALYs, and the cost has been reduced by 19474.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -26569.51 CNY per QALY. Similar results were obtained in various extensive sensitivity analyses.ConclusionsThis is the first study to evaluate the cost-effectiveness of SBP in the treatment of CAD. In conclusion, SBP as an add-on treatment to standard therapy appears to be a cost-effective strategy for CAD in Chinese patients.

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Shexiang Baoxin Pill for Acute Myocardial Infarction: Clinical Evidence and Molecular Mechanism of Antioxidative Stress.

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