Ferroptosis: A novel therapeutic target for diabetic cardiomyopathy

Table 1 Drug targeting of ferroptosis for the treatment of diabetic cardiomyopathy

Drug name	Mechanism of action	Experimental model	Key effects
Ferrostatin-1[64]	Inhibits lipid peroxidation, scavenges free radicals	Mouse DCM model	Anti-oxidative stress, improves myocardial fibrosis
Liproxstatin-1[123]	Stabilizes mitochondrial membrane potential, inhibits lipid ROS generation	Diabetic rat model	Improves cardiac function, inhibits PTGS2 expression
Vitamin E[76]	Lipid-soluble antioxidant, inhibits lipid peroxidation chain reaction	STZ-induced diabetic rats	Reduces myocardial oxidative damage, improves mitochondrial function
CoQ10[77]	Maintains mitochondrial electron transport chain, reduces ROS generation	Diabetic rat model	Enhances myocardial energy metabolism, reduces lipid peroxidation
Resveratrol[122]	Activates Nrf2 pathway, upregulates antioxidant enzymes (e.g., GPX4)	Diabetic mice	Inhibits ferroptosis, reduces apoptosis
Canagliflozin[26]	Promotes the Xc-/GSH/GPX4 axis system	Diabetic mice and high glucose-induced H9C2 cells	Improves mitochondrial dysfunction and alleviates myocardial fibrosis
Sulforaphane[23]	Activates Nrf2 pathway, enhances cellular antioxidant capacity	Diabetic mouse model	Reduces myocardial ferroptosis, improves cardiac remodeling
Curcumin[27]	Enhances the Nrf2/HO-1 pathway	STZ-induced and HFD-fed diabetic mice	Anti-oxidative stress, alleviates and improves myocardial fibrosis
Dexmedetomidine[95]	Activates the Nrf2/GPX4 pathway	HG-induced H9C2 cells	Reduces cardiomyocyte apoptosis
DPP-4 inhibitors (evogliptin)[126]	Blocks NADPH oxidase-mediated ROS generation and lipid peroxidation	db/db mice	Alleviates cardiac lipotoxicity, mitochondrial damage, and fibrosis

DCM: Diabetic cardiomyopathy; ROS: Reactive oxygen species; STZ: Streptozotocin; Nrf2: Nuclear factor erythroid 2-related factor 2; GPX4: Glutathione peroxidase; GSH: Glutathione; NADPH: Nicotinamide adenine dinucleotide phosphate.