Cardamonin protects against diabetic cardiomyopathy by activating macrophage NRF2 signaling through molecular...

Area of Science:

• Cardiovascular Biology
• Pharmacology
• Metabolic Diseases

Background:

• Diabetic cardiomyopathy (DCM) is a major cause of heart failure in diabetic patients.
• Current therapeutic options for DCM are limited.
• Cardamonin (CAD), a flavonoid, exhibits anti-inflammatory and anti-oxidative properties.

Purpose of the Study:

• To investigate the protective effects of Cardamonin (CAD) against diabetic cardiomyopathy (DCM).
• To explore the underlying mechanisms of CAD's action, focusing on macrophage polarization and NRF2 activation.

Main Methods:

• A mouse model of type 2 diabetes was established using streptozotocin and a high-fat diet.
• Mice were treated with CAD via gavage.
• In vitro studies involved treating M1 polarized macrophages with CAD and co-culturing them with cardiomyocytes.
• Molecular docking and surface plasmon resonance assays were used to identify the molecular target of CAD.

Main Results:

• CAD treatment improved hyperglycemia, glucose intolerance, and mitigated cardiac dysfunction, hypertrophy, and apoptosis in diabetic mice.
• CAD significantly inhibited M1 macrophage polarization and subsequent cardiomyocyte injury.
• CAD activated the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant signaling pathway.
• Kelch-like ECH-associated protein 1 (KEAP1) was identified as the molecular target of CAD, and CAD promoted NRF2 nuclear translocation.

Conclusions:

• Cardamonin (CAD) demonstrates significant protective effects against diabetic cardiomyopathy (DCM) in a preclinical model.
• CAD's mechanism involves inhibiting M1 macrophage polarization and activating the NRF2 antioxidant pathway via KEAP1.
• CAD holds promise as a novel therapeutic agent and NRF2 activator for DCM treatment.