Cirsiliol alleviates diabetic cardiomyopathy by inhibiting oxidative stress and improving energy metabolism through the PPAR-α/AMPK pathway

Diabetic cardiomyopathy (DCM) is a core cause of heart failure in diabetic patients, with major pathological features including myocardial energy metabolism disorders, mitochondrial dysfunction, oxidative stress, and inflammatory cascades. This study investigates the mechanism by which the flavonoid compound Cirsiliol improves DCM by regulating the Peroxisome Proliferator-activated Receptor α (PPAR-α)/AMP-activated protein kinase (AMPK) signaling pathway. Using a high-glucose-treated H9C2 myocardial cell model and a streptozotocin-induced diabetic mouse model, the results show that Cirsiliol can dose-dependently increase myocardial cell survival, inhibit high-glucose-induced Apoptosis, and significantly improve cardiac function in diabetic mice. Mechanistic studies indicate that Cirsiliol activates the PPAR-α/AMPK pathway, upregulates the expression of key fatty acid oxidation Enzymes carnitine palmitoyltransferase 1 (CPT1) and p-acetyl-CoA carboxylase (ACC), restores mitochondrial membrane potential, reduces lipid peroxidation product malondialdehyde (MDA) levels, enhances superoxide dismutase activity, and inhibits the release of inflammatory factors such as Interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNF-α). This study elucidates that Cirsiliol intervenes in energy metabolism imbalance, oxidative stress, and inflammatory responses through multiple targets, providing a new strategy for the treatment of DCM.

Cell apoptosis; Cirsiliol; Diabetic cardiomyopathy; Inflammatory response; Oxidative stress; PPAR-α/AMPK.