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

Table 6 Effects of traditional Chinese medicine-derived bioactive compounds on regulating iron metabolism and ferroptosis in diabetic cardiomyopathy

Compounds	Herb source	Drug dosage	Model	Mechanisms
Andrographolide	Green chiretta, Andrographis paniculata (Burm.f.) Wall. ex Nees - Andrographolide	1 mg/kg, 10 mg/kg, 20 mg/kg	STZ-DCM mice; HG-H9c2 cells	Regulates NOX/Nrf2 oxidative stress and NF-κB inflammation/apoptosis[165]
Astragaloside IV	Astragalus, Astragalus membranaceus (Fisch.) Bunge	20 mg/kg/day, 40 mg/kg/day, 80 mg/kg/day (in vivo); 20 μmol/L, 40 μmol/L, 80 μmol/L (in vitro)	STZ-DCM rats, HG-H9c2 cells	↓CD36-mediated lipid uptake; ↓iron overload & lipid peroxidation; ↓ferroptosis markers (ACSL4, PTGS2, MDA); ↑GPX4, SLC7A11; improves cardiac function[166]
Baicalin	Scutellaria baicalensis Georgi (Radix Scutellariae)	100 mg/kg i.g.; 10 LM, 20 LM, and 30 LM in vitro	db/db mice; HG-stimulated cells	Enhances SIRT3 deSUMOylation via SENP1 → restores mitochondrial quality control → inhibits ferroptosis & apoptosis, protects against DCM[160]
Curcumin	Turmeric, Curcuma longa L.	300 mg/kg/day i.g.; 10 μM in vitro	STZ-DCM rabbits; HG/Nor-H9c2 cells	Attenuates ferroptosis via Nrf2/GPX4/HO-1; reduces HG-induced injury[163]
Isoliquiritigenin	Chinese licorice, Glycyrrhiza uralensis Fisch. ex DC.	10 mg/kg, 20 mg/kg i.g. every other day for 12 weeks; 10 μM, 20 μM in vitro	STZ-T1DM mice; HG-H9c2 cells	Enhances Nrf2 activity in high glucose-induced H9c2 cardiomyocyte models[162]
Luteolin	Chinese skullcap, Scutellaria baicalensis Georgi	20 mg/kg i.g. for 15 weeks; 5 and 10 μM in vitro	STZ-DCM mice; HG-H9c2 cells	Enhances Nrf2 activity in high glucose-induced H9c2 cardiomyocyte models[161]
Paeoniflorin	Peony, Paeonia lactiflora Pall.	20 mg/kg/day and 70 mg/kg/day in vivo; 11, 12-EET 1 μM in vitro	STZ-DCM rats; HG-H9c2 cells	Modulates gut microbiota (↑Lactobacillus, Akkermansia; ↑butyrate, indole metabolites); restores NrF2/GPX4 pathway; ↓Fe2+ accumulation, lipid ROS, ACSL4, PTGS2; ↑SLC7A11, GSH; inhibits ferroptosis; improves mitochondrial function and cardiac performance[164]
Schisandrol B	Chinese magnolia vine, Schisandra chinensis (Turcz.) Baill.	12.5 mg/kg, 25 mg/kg (10 weeks)	HFD + STZ-induced diabetic mice, PA-H9C2 cells	Inhibits ferroptosis via p53/SLC7A11/GPX4 axis, improves myocardial lipid metabolism[167]
Sulforaphane	Broccoli (cruciferous vegetables), Brassica oleracea L.	0.5 mg/kg/day (i.p., 12 weeks); 1-5 μM (HG-H9c2 cells)	STZ-DCM mice; HG-H9c2 cells	Regulates ferroptosis via AMPK/Nrf2[124]
Syringaresinol	Clove, Syzygium aromaticum (L.) Merr. & L. M. Perry	Administered i.g. every other day for 8 weeks	STZ-induced type 1 diabetic mice	Alleviates DCM, reduces fibrosis and oxidative stress by downregulating Keap1 and activating Nrf2-NQO1/HO-1[219]

i.p.: Intraperitoneal injection; i.g.: Intragastric administration; DCM: Diabetic cardiomyopathy; STZ: Streptozotocin; HFD: High-fat diet; GSH: Glutathione.