Mechanism of Astragali Radix-Aconiti Lateralis Radix Praeparata in Treatment of Heart Failure Based on UPLC-Q-TOF-MS and Network Pharmacology
10.13422/j.cnki.syfjx.20221612
- VernacularTitle:UPLC-Q-TOF-MS结合网络药理学探讨黄芪-附子治疗心力衰竭的作用机制
- Author:
Xie ZHONG
1
;
Yao ZHANG
1
;
Jun LI
2
;
Han MAO
1
;
Xiangyun CHEN
1
;
Yaofeng LI
1
Author Information
1. School of Basic Medicine， Guizhou University of Traditional Chinese Medicine（TCM）， Guiyang 550025， China
2. Resource Institute for Chinese & Ethnic Materia Medica of Guizhou University of TCM， Guiyang 550025， China
- Publication Type:Journal Article
- Keywords:
heart failure;
Astragali Radix;
Aconiti Lateralis Radix Praeparata;
network pharmacology;
hypoxia-inducible factor-1 （HIF-1） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(3):70-80
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Astragali Radix-Aconiti Lateralis Radix Praeparata in the treatment of heart failure and substance basis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometer （UPLC-Q-TOF-MS） and network pharmacology. MethodThe chemical components of Astragali Radix-Aconiti Lateralis Radix Praeparata solution was analyzed by UPLC-Q-TOF-MS， and the active components and targets were screened out by the PubChem database. The targets related to heart failure disease were retrieved from Comparative Toxicogenomics Database（CTD）， Online Mendelian Inheritance in Man （OMIM）， and GeneCard databases， and the common targets were obtained by Venn analysis. The target protein-protein interactions （PPI） were analyzed using the STRING database. Gene ontology （GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis were performed using the Metascape database， and molecular docking verification of key targets and active components was performed using SYBYL-X 2.1.1. Experimental validation of key targets was carried out using the rat model of heart failure. ResultThere were 202 chemical components identified in Astragali Radix-Aconiti Lateralis Radix Praeparata solution， of which 64 active components were predicted to act on 183 targets for the treatment of heart failure. The important active components were caffeic acid， L-arginine， biochanin A， adenine， nicotinic acid， trans-ferulic acid， p-coumaric acid， riboflavin， calycosin， etc. The main targets were interleukin （IL）-6， cysteine aspartic acid specific protease （Caspase）-3， vascular endothelial growth factor A （VEGFA）， protein kinase B1 （Akt1）， tumor necrosis factor （TNF）， IL-1B， matrix metallopeptidase （MMP）-9， etc. The main signaling pathways involved hypoxia-inducible factor （HIF）-1 signaling pathway， TNF signaling pathway， phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway， Toll-like receptor signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， forkhead box O （FoxO） signaling pathway， etc. The molecular docking results showed that the active components in Astragali Radix-Aconiti Lateralis Radix Praeparata solution had a good binding ability with HIF-1α， VEGFA， Akt1， Caspase-3， and IL-6， which were the key proteins in the HIF-1 signaling pathway. Animal experiments showed that Astragali Radix-Aconiti Lateralis Radix Praeparata solution significantly improved the hemodynamic indexes， reduced the serum atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP）， and IL-6 levels， improved the myocardial histopathological changes， protected the mitochondrial morphology of cardiomyocytes， down-regulated the expression of HIF-1α， VEGFA and phosphorylation（p）-Akt， and reduced the activation of Caspase-3 in the myocardial tissue of rats with heart failure. ConclusionAstragali Radix-Aconiti Lateralis Radix Praeparata treats heart failure in a multi-component， multi-target， and multi-pathway manner. The experimental validation indicates that it treats heart failure by improving myocardial histopathological changes and regulating HIF-1 signaling pathway， which provides references for the subsequent pharmacodynamic substance research.
