Objective: To systematically investigate the mechanism of Huangqi-Huangjing in the treatment of Diabetic Nephropathy (DN) and Diabetic Cardiomyopathy (DC) using network pharmacology and molecular docking analysis. To provide a theoretical basis for the development of new drugs for the treatment of DN and DC.

Methods: The active ingredients and therapeutic targets of Huangqi-Huangjing, DN and DC were predicted and screened using TCMSP, GeneCards, DisGeNet and OMIM databases. Networks of active ingredients and targets were mapped using Cytoscape 3.8.2, Protein-Protein Interactions (PPI) were analyzed using the STRING database, and enrichment analysis of key targets was performed using “clusterProfiler” in R. Molecular docking of active ingredients and key targets was performed by Autodock vina.

Results: A total of twenty-six active drug compounds, including diosgenin, formononetin, 7-O-methyl isomucronulatol, and 207 potential targets of Huangqi-Huangjing were obtained. PPI network analysis showed that targets such as AKT1, JUN, TP53, HSP90AA1 and RELA were associated with both huangqi-huangjing and DN-DC. GO and KEGG pathway analysis showed that most of these targets were involved in pathways such as Th17 cell differentiation, IL-17 signaling pathway, and AGE-
RAGE signaling pathway in diabetic complications. Docking studies showed that diosgenin has ideal binding activity to TP53, RELA and AKT1.

Conclusion: The active ingredients of Huangqi-Huangjing such as diosgenin may act on DN and DC through different targets such as TP53, RELA and AKT1, which can help to develop innovative drugs for effective treatment of DN and DC.