A Bioinformatics Investigation into the Pharmacological Mechanisms of Sodium-Glucose Co-transporter 2 Inhibitors in Diabetes Mellitus and Heart Failure Based on Network Pharmacology

Figures

• 

  Fig. 1. The workflow of the network pharmacology strategies for determining the pharmacological mechanisms of the SGLT2 inhibitors in diabetes with heart failure through cluster and pathway analysis.

• 

  Fig. 2. Interaction network to indicate drug-target composited of 4 SGLT2 inhibitors (blue) and 136 targets (pink).

• 

  Fig. 3. The numbers of SGLT2 inhibitors and diabetes status with heart failure-related targets are shown in the Venn diagram. There were 13,523 targets of HF from the databases (upper left), 15,291 targets of DM from the database (upper right), 283 targets of HF-DM from studies (bottom left), 135 targets of SGLT2 inhibitors (bottom right) and 125 common targets between SGLT2 inhibitors and diabetes status with heart failure.

• 

  Fig. 4. The drug-target-disease networks of SGLT2 inhibitors and diabetes status with heart failure. The yellow nodes represent DM and HF; the green nodes represent four SGLT2 inhibitors; the pink nodes represent 125 common targets.

• 

  Fig. 5. The process of screening core targets by Cytohubba according to degree value. From 125 common targets (left), 33 core targets (right) ranked in the front of the degree value were selected.

• 

  Fig. 6. The protein–protein interaction (PPI) network based on 33 core targets of SGLT2 inhibitors in diabetes status with heart failure. Network nodes represent different proteins. The structures in the nodes are the protein structures. Edges represent protein–protein associations, and the line thickness indicates the strength of data support.

• 

  Fig. 7. Protein interaction relationship histogram of SGLT2 inhibitors.

• 

  Fig. 8. Enrichment analysis of Gene Ontology (GO) biological process of 33 core genes related to SGLT2 inhibitors on diabetes status with heart failure.

• 

  Fig. 9. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for 33 core targets of SGLT2 inhibitors on diabetes status with heart failure.

• 

  Fig. 10. The KEGG pathways of the four drugs were shown in the Venn diagram.