Regulation of ferroptosis and mitochondrial homeostasis disruption in diabetic cardiomyopathy: Therapeutic potential of traditional Chinese medicine

Table 2 Traditional Chinese medicine-derived bioactive compounds that ameliorate mitochondrial homeostasis disruption and ferroptosis

Compounds	Herb source	Drug dosage	Model	Mechanisms	Clinical evidence
Resveratrol	Japanese knotweed, Reynoutria japonica Houtt.	25-50 mg/kg i.g./i.p. (5-7 days); 20-50 μM in vitro	STZ-DCM mice; HG-H9c2 cells	Activating SIRT1 → PGC-1α increases mitochondrial biogenesis (↑mtDNA, ΔΨm, ATP). Additionally, activating the Nrf2-GPX4 axis confers anti-ferroptotic protection; in STZ-T1DM DCM mice, resveratrol (25 mg/kg/day, 12 weeks) ↓labile Fe/MDA, ↑GSH/GPX4, improved EF/FS, and restored mitochondrial ultrastructure[95,139,140]	Clinical studies and systematic reviews report improved insulin resistance, glycemic control, and oxidative stress (15 RCTs, 896 patients)[142-145]
Salidroside	Rhodiola, Rhodiola rosea L.	1.5 g/kg/day i.g. for 5 weeks	db/db mice	Inhibits ferroptosis (↑GPX4; ↓serum iron, transferrin; trend ↓SLC7A11); modulates autophagy (↓LC3-II); improves myocardial ultrastructure[146]
Salidroside	Rhodiola, Rhodiola rosea L.	50-100 mg/kg/day, 16 weeks (oral gavage); 10 μM in vitro	HFD/STZ-DCM mice; NRCMs	Activates AMPK/Akt-SIRT3 → ↑PGC-1α, TFAM; promotes mitochondrial biogenesis; improves mitochondrial function[147]

i.p.: Intraperitoneal injection; i.g.: Intragastric administration; DCM: Diabetic cardiomyopathy; ΔΨm: Mitochondrial membrane potential; T1DM: Type 1 diabetes mellitus; GSH: Glutathione; STZ: Streptozotocin; RCT: Randomized clinical trial; HFD: High-fat diet.