Efficacy and Safety of Shenfu Injection on Acute Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: The adjunctive efficacy and safety of Shenfu Injection (SFI) for acute heart failure (AHF) still remains ambiguous even though previous studies made initial conclusions. OBJECTIVE: To comprehensively evaluate the adjunctive efficacy and safety of SFI in the treatment of AHF. STUDY DESIGN: This was a meta-analysis and systematic review. METHODS: 8 databases were searched for qualified randomized controlled trials (RCTs) from May 1990 to May 2022. The primary results included total clinical effective rate (TCER) and left ventricular ejection fraction (LVEF). The secondary results included left ventricular end diastolic dimension (LVEDD), heart rate (HR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and adverse events (AE). The quality evaluation, meta-analysis, sensitivity analysis, subgroup analysis and publication bias were conducted by RevMan5.3 software. Meta-regression analysis was conducted using Stata software 15.0, and trial sequential analyses (TSA) was performed by TSA program. Finally, the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) system was applied for evaluating the quality of evidence. RESULTS: 61 RCTs containing 5505 AHF patients were included. The meta results demonstrated SFI combined with conventional western treatment (CWT) for AHF was superior to CWT alone in improving the TCER (RR = 1.21; 95% CI (1.18, 1.24); p < 0.001), improving LVEF (SMD = 0.85; 95% CI (0.77,0.92); p < 0.001) and reducing HR (SMD = -0.67; 95% CI (0.80, -0.54) p < 0.001). It had a lower AE rate in the SFI+CWT group (27/753, 3.59%) than the CWT group (68/739, 9.20%) (RR = 0.40; 95% CI (0.26, 0.61); p < 0.001). The outcomes' evidentiary quality of TCER, HR, LVEF and AE were assessed as moderate. CONCLUSION: Adjunctive use of SFI was safer to improve TCER and heart function of AHF, but the results should be interpreted with cautious for clinical practice until high quality-designed RCTs were require for further confirmation due to poor quality of part of the included studies.

Efficacy and safety of Shenfu injection for the treatment of post-acute myocardial infarction heart failure: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to investigate the adjuvant effect and safety of Shenfu injection (SFI) on the treatment of post-acute myocardial infarction heart failure (PAMIHF). Methods: Seven databases were searched to identify randomized controlled trials (RCTs) associated with SFI and PAMIHF treatment from May 1990 to May 2022. Primary outcomes included NT-proBNP and left ventricular ejection fraction (LVEF), and secondary outcomes included total effective rate, BNP, heart rate (HR), cardiac output (CO), and adverse event (AE). The risk of bias evaluation was assessed by the ROB2 tool, meta-analysis, subgroup analysis, sensitivity analysis, and publication bias were conducted by RevMan5.3 software, and the Grade of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence of meta results. Results: A total of 36 studies with 3231 PAMIHF patients were included. The meta results suggested that adjuvant SFI therapy was superior to conventional medical therapy alone. It improved the total effective rate [RR = 1.33; 95% CI (1.25.1.40); p < 0.00001], increased LVEF [SMD = 0.98; 95% CI (0.71, 1.24); p < 0.00001], and decreased HR [SMD = -1.14; 95% CI (-1.28, -0.99); p < 0.00001]. In addition, adjuvant SFI therapy (9.73%, 66/678) had a rate of AE lower than that of conventional medical therapy alone (21.7%, 147/677) when regarding safety [RR = 0.45; 95% CI (0.35, 0.57); p < 0.00001]. The quality of the evidence for the outcomes was rated from "very low" to "moderate." Conclusion: Adjuvant SFI therapy was safer to improve the total effective rate and the heart function of PAMIHF patients. However, well-designed RCTs were needed to confirm the efficacy and safety of adjuvant SFI therapy in PAMIHF treatment due to the low quality of the evidence for the outcomes caused by a small sample size and unclear risk of bias existed in included studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=151856), identifier CRD42020151856.

Identification of natural compounds as SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation.

Background: Base mutations increase the contagiousness and transmissibility of the Delta and Lambda strains and lead to the severity of the COVID-19 pandemic. Molecular docking and molecular dynamics (MD) simulations are frequently used for drug discovery and relocation. Small molecular compounds from Chinese herbs have an inhibitory effect on the virus. Therefore, this study used computational simulations to investigate the effects of small molecular compounds on the spike (S) protein and the binding between them and angiotensin-converting enzyme 2 (ACE2) receptors. Methods: In this study, molecular docking, MD simulation, and protein-protein analysis were used to explore the medicinal target inhibition of Chinese herbal medicinal plant chemicals on SARS-CoV-2. 12,978 phytochemicals were screened against S proteins of SARS-CoV-2 Lambda and Delta mutants. Results: Molecular docking showed that 65.61% and 65.28% of the compounds had the relatively stable binding ability to the S protein of Lambda and Delta mutants (docking score ≤ -6). The top five compounds with binding energy with Lambda and Delta mutants were clematichinenoside AR2 (-9.7), atratoglaucoside,b (-9.5), physalin b (-9.5), atratoglaucoside, a (-9.4), Ochnaflavone (-9.3) and neo-przewaquinone a (-10), Wikstrosin (-9.7), xilingsaponin A (-9.6), ardisianoside G (-9.6), and 23-epi-26-deoxyactein (-9.6), respectively. Four compounds (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) could interact with S protein mutation sites of Lambda and Delta mutants, respectively, and MD simulation results showed that four plant chemicals and spike protein have good energy stable complex formation ability. In addition, protein-protein docking was carried out to evaluate the changes in ACE2 binding ability caused by the formation of four plant chemicals and S protein complexes. The analysis showed that the binding of four plant chemicals to the S protein could reduce the stability of the binding to ACE2, thereby reducing the replication ability of the virus. Conclusion: To sum up, the study concluded that four phytochemicals (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) had significant effects on the binding sites of the SARS-CoV-2 S protein. This study needs further in vitro and in vivo experimental validation of these major phytochemicals to assess their potential anti-SARS-CoV-2. Graphical abstract.

Shenfu injection alleviates the clinical symptoms of heart failure patients combined with conventional treatment: A protocol for systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Shenfu Injection (SFI) is a promising alternative treatment for heart failure (HF) in China. Many complete clinical trials have examined the efficacy of SFI combined use with conventional treatment (CT) vs CT alone. This study is to conduct a systematic review and meta-analysis of randomized clinical trials to evaluate the benefits and risks of using SFI in addition to CT for the treatment of HF. METHOD: All the trials will be searched through 4 English databases (MEDLINE via PubMed, the Cochrane Library, EMBASE, Web of Science) and 4 Chinese databases (the China Science and Technology Journal Database, Chinese Biomedical Literature Database, Wan-fang Database, the China National Knowledge Infrastructure.) from October 2005 to June 2019. Conference articles or articles with incomplete data will be removed. The primary outcome was the New York Heart Association, 6-minute walk test, hospitalization or rehospitalization. Left ventricular ejection fraction percentage, left ventricular end-diastolic dimension, Cardiac index, heart rate, N-terminal pronatriuretic peptide and other indicators were also assessed. RevMan V.5.3 Software and Stata 13.0 Statistics Software were used to calculate the data synthesis and conduct meta-analysis according to the guideline of Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols 2015. RESULTS: Mortality, New York Heart Association function classification, heart rate, 6-minute walk test, hospitalization or rehospitalization, Heart rate, systolic blood pressure, DBP, Cardiac minute volume, left ventricular ejection fractions percentage, left ventricular end-diastolic dimension (mm), N-terminal pronatriuretic peptide, etc. and adverse effects will be comprehensively assessed to evaluate the adjunctive effect of SFI through different aspects. We will perform a meta-analysis of each outcome with subgroup analysis based on the type of HF, treatment methods, and course of disease. Sensitivity analysis will be conducted with clinical factors, treatment methods, methodological characteristics, and statistical heterogeneity (if applicable). CONCLUSION: This study will assess the adjunctive effect of SFI and its safety on HF with clinical evidence. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020151856.

[Meta-analysis of supplemented Zhenwu decoction for treating congestive heart-failure].

The paper was to systematically evaluate the clinical efficacy of supplemented Zhenwu decoction for treating congestive heart-failure. Three foreign language databases including the Cochrane Library, PubMed, EMbase and four Chinese databases including CBM, CNKI, VIP and Wanfang Database were retrieved from their establishment to July 2016 for all randomized control trials(RCTs) on supplemented Zhenwu decoction in treatment of congestive heart-failure. The references in the included RCTs were also traced. Literature selection and information extraction was completed and screened by two independent reviewers, and Meta-analysis was performed by using RevMan 5.3 software. Totally 13 clinical RCTs were included in this study, involving 982 patients. Meta-analysis results showed that as compared with western medicine alone, the total effective rate of heart function could be improved by applying supplemented Zhenwu decoction based on the western medicine[RR=1.16, 95%CI (1.10, 1.22)], with increased ejection fraction[MD=7.12, 95%CI= (3.98,10.27)], increased cardiac activity index[MD=6.92, 95%CI (5.21, 8.62)], increased stroke volume [MD=11.18, 95%CI (6.04, 16.33)], and increased heart index[MD=0.50, 95%CI (-0.29, 1.30)]. Supplemented Zhenwu decoction combined with routine treatment could improve the clinical symptoms of congestive heart-failure. However, due to the low quality in methodology and reports as well as small sample size of included RCTs in this study, more randomized double-blind trials with a large sample size are still required to verify the efficiency of supplemented Zhenwu decoction for treating congestive heart-failure.