Abstract
BACKGROUND: Diabetic cardiomyopathy (DCM), a common cardiovascular complication associated with diabetes mellitus, has the potential to progress to heart failure. Apocynum venetum L. leaves extract (AVLE) possesses known cardioprotective activity, but its effect on DCM remains unclear. This study explored the protective effects of AVLE against myocardial injury in type 2 diabetes and the underlying mechanisms. METHODS: DCM was established in vivo using db/db mice and in vitro using high-glucose, high-fat (HGHF)-stimulated H9c2 cardiomyocytes. We evaluated metabolic profiles, cardiac function, histopathology, oxidative stress, inflammation, and ferroptosis. RESULTS: In vivo, following 12 weeks of AVLE treatment, cardiac function and structural integrity were significantly improved, serum cardiac injury markers and dyslipidemia were reduced, and pathological myocardial remodeling was attenuated in db/db mice; in vitro, AVLE enhanced cell viability and attenuated cellular damage under HGHF conditions. Mechanistically, AVLE alleviated oxidative stress and inflammation, restored mitochondrial function, and inhibited ferroptosis by regulating key pathway proteins; it upregulated GPX4 and SLC7A11, while downregulating TfR1 and ACSL4. CONCLUSIONS: AVLE exerts cardioprotective effects against diabetic cardiomyopathy by reducing oxidative stress and inflammation, mitigating lipid peroxidation and mitochondrial damage, ultimately inhibiting ferroptosis through regulation of the Xc(-)/GSH/GPX4 axis.