Exploration on the Pharmacodynamic Material Basis of Bawei Chenxiang Powder in Treating Coronary Heart Disease Based on Network Pharmacology and Experimental Verification
Objective To investigate the pharmacodynamic material basis of Bawei Chenxiang Powder in the treatment of coronary heart disease.Methods The action targets of 16 blood-entry components of Bawei Chenxiang Powder were retrieved by TCMSP,PharmMapper and SwissTargetPrediction,and the disease targets were found by GeneCards and OMIM databases,which screened the intersection targets of the components and the disease;a component-target network was constructed using Cytoscape 3.9.1 software and key components were screened;the protein-protein interaction network was obtained by using STRING database and core targets were screened;GO and KEGG pathway enrichment analysis of intersecting targets was performed using DAVID database;molecular docking between key components and core targets was performed;molecular dynamics simulations were performed using Amber 20 software;UPLC-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry was used to quantify the key components in rat plasma;the hypoxia/reoxygenation model of H9c2 cells was constructed to investigate the effects of the key components on the survival rate and LDH of H9c2 cells.Results Totally 514 targets of the 16 blood-entry components of Bawei Chenxiang Powder,1716 targets of coronary heart disease,and 192 intersecting targets were retrieved,among which the key components were quercetin,kaempferol,naringenin,dehydrodiisoeugenol,and the core targets were ALB,IL6,TNF,GAPDH,AKT1,IL1B and TP53;the KEGG results showed that the mechanism of Bawei Chenxiang Powder for treating coronary heart disease may be related to PI3K-Akt signaling pathway,MAPK signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,etc.;molecular docking showed that the key components had low binding energy with the core targets;molecular dynamics simulation results showed that the binding energy of TNF and quercetin was tight and stable,with a binding energy of-20.263 3 kcal/mol;the concentrations of the key components in plasma were quercetin(15.65±1.76)ng/mL,kaempferol(10.58±0.96)ng/mL,naringenin(3.07±0.69)ng/mL,and dehydrodiisoeugenol(4.90±1.18)ng/mL;the results of cellular experiments showed that the above four components could significantly increase the survival rate of H9c2 cells under hypoxia/reoxygenation conditions and reduce the LDH activity in the cell supernatant.Conclusion Quercetin,kaempferol,naringenin,dehydrodiisoeugenol and other components in Bawei Chenxiang Powder may be the pharmacodynamic material basis for treating coronary heart disease.
万方数据
