Systematic Evaluation Of Baoyuan Decoction In The Treatment Of Chronic Heart Failure And Its Network Pharmacological Analysis Of Blood Components

Objective(1)Carry out the systematic evaluation of Baoyuan Decoction in the treatment of chronic heart failure to provide evidence-based basis for its clinical rational drug use.(2)Study the molecular mechanism of Baoyuan Decoction in the treatment of chronic heart failure based on blood components and network pharmacology.Methods(1)Clinical systematic evaluationBy searching PubMed,the Cochrane Library,CNKI,VIP,Wanfang digital journal and other databases,collect the clinical randomized controlled trials(RCTs)of Baoyuan Decoction in the treatment of chronic heart failure.The retrieval time is from the establishment time of the database to March 2022.Evaluate the quality of the studies that meet the inclusion criteria and extract the data,Revman 5.3 software was used for Meta analysis.(2)Identification of blood componentsCombined with the existing literature on the analysis of traditional Chinese medicine components of Baoyuan decoction,the chemical components of various herbs of Baoyuan Decoction were searched in tcmsp database,and the compound database of Baoyuan decoction was established.The corresponding medicinal solution and serum samples containing drugs were prepared,and the blood components of Baoyuan Decoction were comprehensively analyzed by ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).(3)Network pharmacological analysisTCMSP database and Swiss Target Prediction data platform are used to predict the target of the identified blood components,and the network visualization software Cytoscape 3.7.2 is used to draw the correlation network diagram.Finally,GO enrichment analysis and KEGG pathway enrichment analysis are carried out for the key targets.Results(1)Systematic evaluation based on Meta analysis12 RCTs were included in this study,with a total sample of 980 cases.The results showed that compared with the conventional treatment of Western medicine,the combination of Baoyuan decoction could improve the clinical efficacy[RR=1.25,95%CI(1.17,1.32),P<0.00001],increase the level of left ventricular ejection fraction(LVEF)[MD=4.71,95%CI(2.35,7.07),P<0.0001],decrease the level of B-type natriuretic peptide precursor(pro-BNP)[MD=-953.48,95%CI(-1000.96,-906.01),P<0.00001],decreased the level of B-type natriuretic peptide(BNP)[MD=-191.66,95%CI(-195.14,-188.18),P<0.00001].(2)Identification of blood components based on UHPLC-Q-TOF/MS technology.Explore the chromatographic conditions:Waters ACQUITY UPLC BEH C18 chromatographic column(2.1mm×100mm,1.7μm);Mobile phase A(0.1%formic acid water)-B(acetonitrile),gradient elution,flow rate 0.3mL/min;Column temperature 30℃,the injection volume of compound recognition in vitro was 1μL,the injection volume for blood component identification is 5μL,detection wavelength:254nm.Mass spectrometry conditions:data acquisition range 100～1700m/z,ion source temperature 350℃,capillary voltage 3.5kV(positive ion mode)and 4.0kV(negative ion mode),atomization gas pressure 45psi,dry gas flow rate 11L/min,sheath gas flow rate 11L/min,sheath gas temperature 350℃,fragment voltage 140V.Based on the 94 chemical components identified in vitro of Baoyuan decoction,27 blood components were identified,including 5 compounds such as Ginsenoside Rb1 and Re from Ginseng,10 compounds such as Formononetin,Ononin,Calycosin from Astragalus membranaceus,9 compounds such as Liquiritin,Isoliquiritin and Glycyrrhizic acid from Licorice,and 3 compounds such as Hypnone from Cinnamomum cassia.(3)Research on the mechanism of action based on network pharmacologyThere are 55 targets related to chronic heart failure,including TNF,IL-6,IL-2,NR3C1 and other inflammatory factors;EGFR,MTOR,ERBB2 and other cell proliferation factors;SRC,MAPK family and other tyrosine kinases;VEGFA,PTGS2,NOS2 and other cardiovascular targets;STAT3 and PRKCA as blood circulation,vascular and blood pressure regulation,cell proliferation regulation,and regulate relaxin signaling pathway,VEGF signaling pathway,fluid shear stress and atherosclerosis,IL-17 signaling pathway,AGE-RAGE signaling pathway and so on.ConclusionBaoyuan Decoction is effective in the treatment of chronic heart failure.It mainly regulates biological processes such as blood circulation,blood vessel and blood pressure regulation,cell proliferation regulation,and regulates HIF-1,PI3K Akt,AGE-RAGE and other pathways to reduce the damage of cardiomyocytes.It has pharmacological effects such as anti-inflammatory,anti myocardial hypoxia and improving energy metabolism,so as to achieve the effect of treating chronic heart failure.