Molecular Mechanism of Medicinal Pair Astragali Radix-Angelicae Sinensis Radix Against Diabetic Cardiomyopathy / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the action mechanism of medicinal pair Astragali Radix-Angelicae Sinensis Radix against diabetic cardiomyopathy （DCM） based on network pharmacology and<italic> in vivo </italic>animal experiment. Method:The active ingredients and targets of Astragali Radix and Angelicae Sinensis Radix were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）， and the relevant targets of DCM from the disease database. The common specific targets between the medicinal pair and DCM obtained via comparison were used for constructing the main active ingredients of Astragali Radix-Angelicae Sinensis Radix-DCM-target network， followed by protein-protein interaction （PPI） analysis of compound-DCM common targets and the screening of important modules using Molecular Complex Detection （MCODE） plugin. The gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis was carried out based on DAVID for exploring the possible molecular mechanisms， which were then subjected to experimental verification. Result:A total of 126 core targets of Astragali Radix-Angelicae Sinensis Radix for treating DCM were screened out based on network pharmacology. As indicated by KEGG pathway enrichment analysis， the above-mentioned key targets might be related to such pathways as inflammatory response， oxidative stress， insulin resistance， and apoptosis. The findings of <italic>in vivo</italic> animal experiments demonstrated that Astragali Radix-Angelicae Sinensis Radix delayed high glucose-induced cardiomyocyte injury of DCM rats， suggesting that this medicinal pair intervened in the pathological process to a certain extent. Conclusion:Astragali Radix-Angelicae Sinensis Radix alleviates DCM possibly by acting on multiple targets including interleukin-6， vascular endothelial growth factor A， tumor necrosis factor， TP53 gene， and nuclear transcription factor， regulating apoptosis and glucolipid metabolism， and improving oxidative stress and inflammatory response. The research based on network pharmacology and experimental verification has provided new ideas for investigating the pathogenesis of DCM and its clinical treatment.