Table2_Preclinical Evidence of Paeoniflorin Effectiveness for the Management of Cerebral Ischemia/Reperfusion Injury: A Systematic Review and Meta-Analysis.DOCX

Background: Vessel recanalization is the main treatment for ischemic stroke; however, not all patients benefit from it. This lack of treatment benefit is related to the accompanying ischemia-reperfusion (I/R) injury. Therefore, neuroprotective therapy for I/R Injury needs to be further studied. Paeonia lactiflora Pall. is a commonly used for ischemic stroke management in traditional Chinese medicine; its main active ingredient is paeoniflorin (PF). We aimed to determine the PF’s effects and the underlying mechanisms in instances of cerebral I/R injury.Methods: We searched seven databases from their inception to July 2021.SYRCLE’s risk of bias tool was used to assess methodological quality. Review Manager 5.3 and STATA 12.0 software were used for meta-analysis.Results: Thirteen studies, including 282 animals overall, were selected. The meta-analyses showed compared to control treatment, PF significantly reduced neurological severity scores, cerebral infarction size, and brain water content (p = 0.000). In the PF treatment groups, the apoptosis cells and levels of inflammatory factors (IL-1β) decreased compared to those in the control groups (p = 0.000).Conclusion: Our results suggest that PF is a promising therapeutic for cerebral I/R injury management. However, to evaluate the effects and safety of PF in a more accurate manner, additional preclinical studies are necessary.</p

Table1_Preclinical Evidence of Paeoniflorin Effectiveness for the Management of Cerebral Ischemia/Reperfusion Injury: A Systematic Review and Meta-Analysis.XLSX

Background: Vessel recanalization is the main treatment for ischemic stroke; however, not all patients benefit from it. This lack of treatment benefit is related to the accompanying ischemia-reperfusion (I/R) injury. Therefore, neuroprotective therapy for I/R Injury needs to be further studied. Paeonia lactiflora Pall. is a commonly used for ischemic stroke management in traditional Chinese medicine; its main active ingredient is paeoniflorin (PF). We aimed to determine the PF’s effects and the underlying mechanisms in instances of cerebral I/R injury.Methods: We searched seven databases from their inception to July 2021.SYRCLE’s risk of bias tool was used to assess methodological quality. Review Manager 5.3 and STATA 12.0 software were used for meta-analysis.Results: Thirteen studies, including 282 animals overall, were selected. The meta-analyses showed compared to control treatment, PF significantly reduced neurological severity scores, cerebral infarction size, and brain water content (p = 0.000). In the PF treatment groups, the apoptosis cells and levels of inflammatory factors (IL-1β) decreased compared to those in the control groups (p = 0.000).Conclusion: Our results suggest that PF is a promising therapeutic for cerebral I/R injury management. However, to evaluate the effects and safety of PF in a more accurate manner, additional preclinical studies are necessary.</p

Table_1_Guanxinning Injection Combined With Ischemic Postconditioning Attenuate Myocardial Ischemic Reperfusion Injury in Chronic Renal Failure Rats by Modulating Mitochondrial Dynamics.DOCX

PurposeSalvia miltiorrhiza Bge. (Danshen, DS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) have been widely used in traditional Chinese medicine to prevent and treat myocardial ischemia and renal insufficiency, and their extracts (Guanxinning injection, GXN) have been reported to exhibit antioxidant, anti-inflammatory, and anti-ischemia-reperfusion injury properties. It is well-established that ischemic postconditioning (IPOC) can protect against myocardial ischemia-reperfusion (I/R) injury in rats with chronic renal failure (CRF). However, little is known on whether GXN combined with IPOC may affect myocardial I/R injury in CRF rats. We sought to observe the effect of GXN combined with IPOC on myocardial I/R injury in CRF rats by quantifying changes in the expression of proteins related to mitochondrial dynamics.Materials and MethodsIn a survey, 90 Wistar rats were randomly divided into 6 groups (15 rats per group): CRF group, I/R group, comorbid group (CRF + I/R), IPOC group, IPOC + GXN group and the sham group. Changes in blood myocardial injury markers, urea, and creatinine were analyzed. Heart tissues were harvested for histomorphometry and western blotting when rats were sacrificed. Myocardial infarction area was measured by Evans blue and Triphenyltetrazolium chloride solution staining. The expressions of mitochondrial fission relative proteins (DRP1 and FIS1) and mitochondrial fusion relative proteins (OPA1 and MFN1) were detected by western blotting.ResultsIPOC could significantly decrease myocardial injury markers and myocardial area of necrosis (AN)/area at risk (AAR) of the comorbid model rats. Further results showed that GXN combined with IPOC could significantly reduce CK-MB levels and myocardial AN/AAR in comorbid model rats compared with the IPOC group. Meanwhile, both IPOC and IPOC + GXN significantly reduced DRP1 levels and increased the MFN1 and OPA1 protein levels in the comorbid model rats. However, compared with the IPOC group, MFN1 and OPA1 protein levels increased significantly in the IPOC + GXN group.ConclusionExtracts of DS and CX combined with IPOC exert a protective effect against myocardial I/R injury in rats with CRF, mediated by increased expression of mitochondrial fusion proteins (MFN1 and OPA1).</p

Table_2_Guanxinning Injection Combined With Ischemic Postconditioning Attenuate Myocardial Ischemic Reperfusion Injury in Chronic Renal Failure Rats by Modulating Mitochondrial Dynamics.DOCX

PurposeSalvia miltiorrhiza Bge. (Danshen, DS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) have been widely used in traditional Chinese medicine to prevent and treat myocardial ischemia and renal insufficiency, and their extracts (Guanxinning injection, GXN) have been reported to exhibit antioxidant, anti-inflammatory, and anti-ischemia-reperfusion injury properties. It is well-established that ischemic postconditioning (IPOC) can protect against myocardial ischemia-reperfusion (I/R) injury in rats with chronic renal failure (CRF). However, little is known on whether GXN combined with IPOC may affect myocardial I/R injury in CRF rats. We sought to observe the effect of GXN combined with IPOC on myocardial I/R injury in CRF rats by quantifying changes in the expression of proteins related to mitochondrial dynamics.Materials and MethodsIn a survey, 90 Wistar rats were randomly divided into 6 groups (15 rats per group): CRF group, I/R group, comorbid group (CRF + I/R), IPOC group, IPOC + GXN group and the sham group. Changes in blood myocardial injury markers, urea, and creatinine were analyzed. Heart tissues were harvested for histomorphometry and western blotting when rats were sacrificed. Myocardial infarction area was measured by Evans blue and Triphenyltetrazolium chloride solution staining. The expressions of mitochondrial fission relative proteins (DRP1 and FIS1) and mitochondrial fusion relative proteins (OPA1 and MFN1) were detected by western blotting.ResultsIPOC could significantly decrease myocardial injury markers and myocardial area of necrosis (AN)/area at risk (AAR) of the comorbid model rats. Further results showed that GXN combined with IPOC could significantly reduce CK-MB levels and myocardial AN/AAR in comorbid model rats compared with the IPOC group. Meanwhile, both IPOC and IPOC + GXN significantly reduced DRP1 levels and increased the MFN1 and OPA1 protein levels in the comorbid model rats. However, compared with the IPOC group, MFN1 and OPA1 protein levels increased significantly in the IPOC + GXN group.ConclusionExtracts of DS and CX combined with IPOC exert a protective effect against myocardial I/R injury in rats with CRF, mediated by increased expression of mitochondrial fusion proteins (MFN1 and OPA1).</p

Table4_Investigating the cardioprotective effects of Fuzheng Yangxin recipe based on network pharmacology and experimental evaluation.XLSX

Background: Under Chinese medicine theory guidance, Fuzheng Yangxin Recipe (FZYX) is clinically effective for the treatment of heart failure (HF) caused by ischemic heart disease (IHD). This study aimed to investigate the mechanism of the myocardial protective effects of FZYX on HF.Materials and methods: The Gene expression omnibus database was used to identify differential genes of the IHD subtype. Through network pharmacological methods, the targets of the active components of FZYX were obtained. We also constructed IHD-induced HF model rats by ligating the left anterior descending coronary artery. Echocardiography, pathological section staining, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and quantitative real-time PCR analyses were performed to verify the protective effects of FZYX on the myocardium.Results: We identified 53 active components and 37 potential targets of FZYX associated with the IHD subtype. Signal transducer and activator of transcription 3 (STAT3) is a key protein in the protein-protein interaction (PPI) network. A total of 146 biological processes, 10 cellular components and 40 molecular function subcategories were identified by Gene Ontology (GO) enrichment analysis, and 18 signalling pathways, including apoptosis, were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In vivo experiments showed that FZYX significantly inhibited cardiomyocyte apoptosis, promoted the expression and phosphorylation of STAT3, and improved cardiac function.Conclusion: FZXY improves cardiac function and protects cardiomyocytes from injury via multi-component, multi-target and multi-pathway action, especially its possible role in regulating STAT3 expression and anti-apoptotic effect.</p

Table5_Investigating the cardioprotective effects of Fuzheng Yangxin recipe based on network pharmacology and experimental evaluation.XLSX

Background: Under Chinese medicine theory guidance, Fuzheng Yangxin Recipe (FZYX) is clinically effective for the treatment of heart failure (HF) caused by ischemic heart disease (IHD). This study aimed to investigate the mechanism of the myocardial protective effects of FZYX on HF.Materials and methods: The Gene expression omnibus database was used to identify differential genes of the IHD subtype. Through network pharmacological methods, the targets of the active components of FZYX were obtained. We also constructed IHD-induced HF model rats by ligating the left anterior descending coronary artery. Echocardiography, pathological section staining, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and quantitative real-time PCR analyses were performed to verify the protective effects of FZYX on the myocardium.Results: We identified 53 active components and 37 potential targets of FZYX associated with the IHD subtype. Signal transducer and activator of transcription 3 (STAT3) is a key protein in the protein-protein interaction (PPI) network. A total of 146 biological processes, 10 cellular components and 40 molecular function subcategories were identified by Gene Ontology (GO) enrichment analysis, and 18 signalling pathways, including apoptosis, were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In vivo experiments showed that FZYX significantly inhibited cardiomyocyte apoptosis, promoted the expression and phosphorylation of STAT3, and improved cardiac function.Conclusion: FZXY improves cardiac function and protects cardiomyocytes from injury via multi-component, multi-target and multi-pathway action, especially its possible role in regulating STAT3 expression and anti-apoptotic effect.</p

Image1_Mechanisms and Efficacy of Traditional Chinese Medicine in Heart Failure.TIF

Heart failure (HF) is one of the main public health problems at present. Although some breakthroughs have been made in the treatment of HF, the mortality rate remains very high. However, we should also pay attention to improving the quality of life of patients with HF. Traditional Chinese medicine (TCM) has a long history of being used to treat HF. To demonstrate the clinical effects and mechanisms of TCM, we searched published clinical trial studies and basic studies. The search results showed that adjuvant therapy with TCM might benefit patients with HF, and its mechanism may be related to microvascular circulation, myocardial energy metabolism, oxidative stress, and inflammation.</p

Table1_Investigating the cardioprotective effects of Fuzheng Yangxin recipe based on network pharmacology and experimental evaluation.XLSX

Background: Under Chinese medicine theory guidance, Fuzheng Yangxin Recipe (FZYX) is clinically effective for the treatment of heart failure (HF) caused by ischemic heart disease (IHD). This study aimed to investigate the mechanism of the myocardial protective effects of FZYX on HF.Materials and methods: The Gene expression omnibus database was used to identify differential genes of the IHD subtype. Through network pharmacological methods, the targets of the active components of FZYX were obtained. We also constructed IHD-induced HF model rats by ligating the left anterior descending coronary artery. Echocardiography, pathological section staining, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and quantitative real-time PCR analyses were performed to verify the protective effects of FZYX on the myocardium.Results: We identified 53 active components and 37 potential targets of FZYX associated with the IHD subtype. Signal transducer and activator of transcription 3 (STAT3) is a key protein in the protein-protein interaction (PPI) network. A total of 146 biological processes, 10 cellular components and 40 molecular function subcategories were identified by Gene Ontology (GO) enrichment analysis, and 18 signalling pathways, including apoptosis, were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In vivo experiments showed that FZYX significantly inhibited cardiomyocyte apoptosis, promoted the expression and phosphorylation of STAT3, and improved cardiac function.Conclusion: FZXY improves cardiac function and protects cardiomyocytes from injury via multi-component, multi-target and multi-pathway action, especially its possible role in regulating STAT3 expression and anti-apoptotic effect.</p

Data_Sheet_1_Effect of arotinolol on chronic heart failure: A systematic review and meta-analysis of randomized controlled trials.pdf

BackgroundHeart failure is the end stage of all cardiovascular diseases, which brings a heavy burden to the global health network. Arotinolol, as a new type of β Receptor blocker, has a good antihypertensive effect. Many clinical trials have observed the clinical efficacy of arotinolol in the treatment of essential hypertension. However, so far, there has been no systematic evaluation on the efficacy and safety of arotinolol in the treatment of chronic heart failure.ObjectiveThe purpose of this review was to systematically evaluate the clinical efficacy of arotinolol in patients with chronic heart failure.MethodsRandomized controlled trials (RCTs) of arotinolol in the treatment of chronic heart failure were retrieved from seven databases according to the Cochrane manual, including CNKI (China National Knowledge Infrastructure), Wan fang database, VIP database, PubMed, Sinomed, EMBASE, and the Cochrane Library databases. The main outcomes were the effective rate, left ventricular ejection fraction (LVEF), blood pressure, heart rate, cardiac index, stroke volume (SV), brain natriuretic peptide (BNP), hypersensitive C-reactive protein (Hs-CRP), left ventricular end diastolic volume (LVEDV), left ventricular end diastolic diameter (LVEDD), and adverse events (AEs).ResultsA total of 17 trials met the qualification criteria, which included 1,717 patients with heart failure. Most trials had uncertain risks in terms of random sequence generation, allocation hiding, patient loss, and result evaluation. Meta analysis showed that arotinolol significantly improved the treatment efficiency of patients with heart failure (standardized mean difference (SMD) = 4.07, 95% confidence interval (CI) [2.89, 5.72], p = 0.00, I2 = 0), LVEF (SMD = 1.59, 95% CI [0.99, 2.19], p = 0.000 0, I2 = 95.8%), cardiac index (SMD = 0.32, 95% CI [0.11, 0.53], p = 0.03), I2 = 0), SV (SMD = 2.00, 95% CI [1.57, 2.34], p = 0.000, I2 = 64.2%), lower BNP (SMD = −0.804, 95% CI [−0.97, −0.64], p = 0.000, I2 = 94.4%), and LVEDV (SMD = −0.25, 95% CI [−0.45, −0.05], p = 0.015, I2 = 0). There was no statistical significance for blood pressure (SMDsystolic pressure = −0.09, 95% CI [−0.69, 0.51], p = 0.775, I2systolic pressure = 90.2%; SMDdiastolic pressure = −0.16, 95% CI [−0.79, 0.48], P = 0.632, I2diastolic pressure = 91.2%), heart rate (SMD = −0.12, 95% CI [−1.00, 0.75], P = 0.787, I2 = 96.1%), Hs-CRP (SMD = −1.52, 95% CI [−3.43, 0.40], P = 0.121, I2 = 98.3%), and LVEDD (SMD = −0.07, 95% CI [−0.90, 0.76], P = 0.870, I2 = 96.5%).ConclusionArotinolol can safely and effectively improve the effective rate of patients with chronic heart failure, increase LVEF, increase CI and SV, and reduce BNP and LVEDV. However, because of the low overall quality of the included randomized controlled trials, these findings need to be considered carefully. More high-quality randomized controlled trials are needed for further verification, to provide a more scientific basis for the safety and effectiveness of arotinolol in the clinical treatment of heart failure.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371214], identifier [CRD:420223371214].</p

Image2_Mechanisms and Efficacy of Traditional Chinese Medicine in Heart Failure.TIF

Heart failure (HF) is one of the main public health problems at present. Although some breakthroughs have been made in the treatment of HF, the mortality rate remains very high. However, we should also pay attention to improving the quality of life of patients with HF. Traditional Chinese medicine (TCM) has a long history of being used to treat HF. To demonstrate the clinical effects and mechanisms of TCM, we searched published clinical trial studies and basic studies. The search results showed that adjuvant therapy with TCM might benefit patients with HF, and its mechanism may be related to microvascular circulation, myocardial energy metabolism, oxidative stress, and inflammation.</p