Background:
Diabetic cardiomyopathy (DCM) is a common diabetes complication with limited
medications. Gegen Qinlian decoction (GQD) has been used in the treatment of diabetes and its related complications
in China for several decades.
Objective:
In this study, network pharmacology was employed to predict the active ingredients, key targets,
and pathways involved in the treatment of DCM by GQD and to validate it by animal experiments.
Methods:
The active ingredients of GQD were retrieved from TCMSP and published literature. DCM-related
gene targets were searched in Drugbank, Genecards, Disgenet, and OMIM disease databases. Protein-protein
interaction networks were constructed using the STRING database and Cytoscape. GO analysis and KEGG
pathway enrichment analysis were performed using the Metascape platform. Moreover, a diabetic mouse
model was established to evaluate the therapeutic effects of GQD by measuring serum biochemical markers
and inflammation levels. Finally, the expression of predicted key target genes was determined using real-time
quantitative PCR.
Results:
A total of 129 active ingredients were screened from GQD. Moreover, 146 intersecting genes related
to DCM were obtained, with key targets, including AKT1, TNF, IL6, and VEGFA. Lipid and atherosclerosis,
AGE-RAGE, PI3K-AKT, and MAPK pathways were identified. Blood glucose control, decreased inflammatory
factors, and serum CK-MB levels were restored after GQD intervention, and the same occurred with the
expressions of PPAR-γ, AKT1, APOB, and GSK3B genes.
Conclusion:
Quercetin, kaempferol, wogonin, 7-methoxy-2-methyl isoflavone, and formononetin may exert
major therapeutic effects by regulating key factors, such as AKT1, APOE, and GSK3B, in the inflammatory
reaction, glycolipid oxidation, and glycogen synthesis related signaling pathways.