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

Table 8 Application prospects of traditional Chinese medicine formulations in diabetic cardiomyopathy

TCM formulation	Formulation composition	Drug dosage	Model	mechanisms
Ginseng Dingzhi decoction	Ginseng, Panax ginseng C. A. Meyer; Atractylodes macrocephala, Atractylodes macrocephala Koidz.; Poria cocos, Poria cocos (Schw.) Wolf; Chinese yam, Dioscorea opposita Thunb.; Xylooligosaccharides	30 g/kg/day, 15 days	TAC-induced heart failure mice; high-glucose-treated HL-1 cells	Mediated inflammation and cardiomyocyte apoptosis; reduces mitochondrial ROS accumulation and restores redox balance; preserves mitochondrial homeostasis and energy metabolism; promotes TMBIM6-dependent PINK/Parkin-mediated mitophagy and suppresses excessive mitochondrial fission; ultimately attenuates myocardial fibrosis and improves cardiac function after TAC[171]
Fufang Zhenzhu Tiaozhi	Ligustri lucidi fructus, Citri sarcodactylis fructus, Eucommiae cortex, Atractylodis macrocephalae rhizoma, Salviae miltiorrhizae radix et rhizoma, Notoginseng radix et rhizoma, Coptidis rhizome and Cirsii japonici herba et radix	0.6 g/kg/day, 1.2 g/kg/day, and 2.4 g/kg/day, 12 weeks	C57BL/6J diabetic mice	Regulates myocardial lipid metabolism and mitochondrial dynamics (↓CD36, ↓mitochondrial lipid overload; ↓Drp1-mediated fission, ↑mitochondrial fusion; ↑mitochondrial energy metabolism); attenuates lipotoxicity-induced apoptosis (↓Bax, ↓cleaved caspase-3; ↓TUNEL-positive cells)[172]
Taohuajing	Persicae Semen [Prunus persica (L.) Batsch], Polygonatum sibiricum Delar. ex Redouté, and Carthami Flos (Carthamus tinctorius L.)	0.125 g/kg/day, 0.25 g/kg/day, and 0.5 g/kg/day, 12 weeks	C57BL/6 J mice with DCM	Activates SIRT1-mediated antioxidant defense (↑SIRT1, ↑GSH-Px, ↑SOD; ↓ROS, ↓MDA); suppresses NLRP3 inflammasome-driven inflammation (↓NLRP3, ↓pro-inflammatory cytokines); attenuates oxidative stress- and inflammation-induced cardiac dysfunction and fibrosis in DCM
YuNü-Jian	Rehmanniae Radix [Rehmannia glutinosa (Gaertn.) DC.]; Anemarrhenae Rhizoma (Anemarrhena asphodeloides Bunge); Gypsum Fibrosum; Ophiopogonis Radix [Ophiopogon japonicus (L. f.) Ker Gawl.]; Achyranthis Bidentatae Radix (Achyranthes bidentata Blume)	4.52 g/kg/day, 10 weeks	Male SD rats with T2DM	Activates the SIRT1-Nrf2-NQO1 antioxidant axis (↑SIRT1, ↑Nrf2, ↑NQO1, ↑SOD, ↑GSH-Px; ↓ROS, ↓MDA); suppresses NLRP3 inflammasome-mediated inflammation; mitigates oxidative stress-associated cardiac fibrosis and remodeling in diabetes-related cardiomyopathy[174]
Ling-Gui-Zhu-Gan decoction	Poria [Poria cocos (Schw.) Wolf]; Cinnamomi ramulus [Cinnamomum cassia (L.) J. Presl]; Atractylodis Macrocephalae Rhizoma (Atractylodes macrocephala Koidz.); Glycyrrhizae Radix et Rhizoma (Glycyrrhiza uralensis Fisch.)	2.1 g/kg/day, 4.2 g/kg/day, and 8.4 g/kg/day, 8 weeks	HFD-induced metabolic cardiomyopathy model-SD rats	r Reduces excessive fatty acid uptake and lipid deposition; Regulates PLIN5-dependent lipid droplet homeostasis; Suppresses lipid peroxidation-driven ferroptosis (↓ACSL4, ↓MDA, ↓lipid peroxidation; ↑GPX4, ↑FPN1, ↑SOD); Preserves mitochondrial structure and function; Attenuates cardiomyocyte injury and cardiac remodeling[175]

TCM: Traditional Chinese medicine; ROS: Reactive oxygen species; DCM: Diabetic cardiomyopathy; GSH: Glutathione; SD: Sprague-Dawley; HFD: High-fat diet.