A network pharmacology analysis identified 21 core overlapping targets between SGLT2 inhibitors and HFpEF, suggesting therapeutic effects through multiple synergistic pathways.
Network pharmacology analysis suggests SGLT2 inhibitors may treat HFpEF through direct or indirect synergy of multiple targets and pathways, including cAMP, MAPK, and calcium signaling.
BACKGROUND: More and more evidence indicates sodium-glucose co-transporter 2 inhibitors (SGLT2is) may display clinical benefits for heart failure with preserved ejection fraction (HFpEF). However, the mechanisms of the action remain unclear. METHODS: A systematic pharmacology-based strategy was applied for predicting the potential molecular mechanisms of SGLT2is in HFpEF. The potential targets of SGLT2is and HFpEF were contained from diverse databases. After networks were constructed, Metascape was applied to functional enrichment. Moreover, the key findings were validated through molecular docking. RESULTS: We obtained 487 SGLT2is related targets and 1505 HFpEF related targets. The networks showed the complex relationship of HFpEF-target-HFpEF. The results of functional enrichment analysis suggested that several biological processes, including muscle system process, inflammatory response, vasculature development, heart development, regulation of MAPK cascade, positive regulation of ion transport, negative regulation of cell population proliferation, cellular response to nitrogen compound, apoptotic signaling pathway, multicellular organismal homeostasis, response to oxidative stress, regulation of cell adhesion, positive regulation of cell death, response to growth factor, and cellular response to lipid, and signaling pathways, such as cardiomyopathy, cAMP signaling pathway, cytokine-cytokine receptor interaction, apoptosis, MAPK signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and NF-kappa B signaling pathway. Finally, we validated the interactions and combinations of SGLT2is and core targets. CONCLUSION: SGLT2is play the potential role of anti-HFpEF through the direct or indirect synergy of multiple targets and pathways. Our study promotes the explanation of the molecular mechanisms of SGLT2is in HFpEF.
Liang et al. (Fri,) conducted a other in Heart failure with preserved ejection fraction (HFpEF). Sodium-glucose co-transporter 2 inhibitors (SGLT2is) was evaluated on Identification of overlapping targets and pathways between SGLT2is and HFpEF. A network pharmacology analysis identified 21 core overlapping targets between SGLT2 inhibitors and HFpEF, suggesting therapeutic effects through multiple synergistic pathways.