Related Experiment Video
Updated: Dec 21, 2025
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Empagliflozin protects heart from inflammation and energy depletion via AMPK activation
Chintan N Koyani1, Ioanna Plastira2, Harald Sourij3
1Division of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Aims:
Sodium-glucose co-transporter 2 (SGLT2) were originally developed as kidney-targeting anti-diabetic drugs. However, due to their beneficial cardiac off-target effects (as SGLT2 is not expressed in the heart), these antagonists currently receive intense clinical interest in the context of heart failure (HF) in patients with or without diabetes mellitus (DM). Since the mechanisms by which these beneficial effects are mediated are still unclear yet, inflammation that is present in DM and HF has been proposed as a potential pharmacological intervention strategy. Therefore, we tested the hypothesis that the SGLT2 inhibitor, empagliflozin, displays anti-inflammatory potential along with its glucose-lowering property.
Methods And Results:
Lipopolysaccharide (LPS) was used to induce inflammation in vitro and in vivo. In cardiomyocytes and macrophages empagliflozin attenuated LPS-induced TNFα and iNOS expression. Analysis of intracellular signalling pathways suggested that empagliflozin activates AMP kinase (AMPK) in both cell types with or without LPS-treatment. Moreover, the SGLT2 inhibitor increased the expression of anti-inflammatory M2 marker proteins in LPS-treated macrophages. Additionally, empagliflozin-mediated AMPK activation prevented LPS-induced ATP/ADP depletion. In vivo administration of LPS in mice impaired cardiac contractility and aortic endothelial relaxation in response to acetylcholine, whereby co-administration of empagliflozin preserved cardiovascular function. These findings were accompanied by improved cardiac AMPK phosphorylation and ATP/ADP, reduced cardiac iNOS, plasma TNFα and creatine kinase MB levels.
Conclusion:
Our data identify a novel cardio protective mechanism of SGLT2 inhibitor, empagliflozin, suggesting that AMPK activation-mediated energy repletion and reduced inflammation contribute to the observed cardiovascular benefits of the drug in HF.
Insights
Sodium-glucose co-transporter 2 (SGLT2) inhibitors like empagliflozin show anti-inflammatory effects. This study suggests empagliflozin protects the heart by activating AMPK, reducing inflammation, and restoring energy levels in heart failure models.
Area of Science:
- Cardiology
- Pharmacology
- Metabolic Diseases
Background:
- Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for diabetes, exhibit beneficial cardiac effects independent of glucose lowering.
- The precise mechanisms behind these cardiovascular benefits, particularly in heart failure (HF), remain incompletely understood.
- Inflammation is a common factor in both diabetes mellitus (DM) and HF, suggesting it as a potential therapeutic target.
Purpose of the Study:
- To investigate the anti-inflammatory potential of the SGLT2 inhibitor empagliflozin.
- To explore whether empagliflozin's cardiovascular benefits are linked to its anti-inflammatory properties and effects on cellular energy metabolism.
- To test the hypothesis that empagliflozin possesses anti-inflammatory effects beyond its glucose-lowering action.
Main Methods:
- In vitro studies using cardiomyocytes and macrophages exposed to lipopolysaccharide (LPS) to induce inflammation.
- Analysis of intracellular signaling pathways, including AMP-activated protein kinase (AMPK) activation and ATP/ADP levels.
- In vivo studies in mice subjected to LPS challenge, assessing cardiovascular function, cardiac energetics, and inflammatory markers.
Main Results:
- Empagliflozin attenuated LPS-induced TNFα and iNOS expression in cardiomyocytes and macrophages.
- Empagliflozin activated AMPK in both cell types and increased anti-inflammatory M2 marker expression in macrophages.
- In vivo, empagliflozin preserved cardiac contractility and endothelial function, reduced cardiac inflammation, and improved cardiac energy status (ATP/ADP).
Conclusions:
- Empagliflozin demonstrates significant anti-inflammatory effects, contributing to its cardiovascular protective properties.
- AMPK activation and subsequent energy repletion appear to be key mechanisms underlying empagliflozin's benefits in HF.
- These findings suggest a novel cardio-protective pathway for SGLT2 inhibitors involving inflammation reduction and metabolic support.
More Related Videos
05:58Mouse Electroacupuncture Fixation Device Fabrication for Electroacupuncture Pretreatment in Diabetic Cardiomyopathy Mouse Model
Published on: April 18, 2025
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Related Concept Videos
01:25cAMP-dependent Protein Kinase Pathways
01:23Dipeptidyl Peptidase 4 Inhibitors
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:30Heart Failure V: Medical Management
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones