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Research Progress on the Role of Traditional Chinese Medicine in Regulating Ferroptosis in Cardiovascular Diseases
Pan Li1, Zi-Meng Qi1, Shi-Chang Li1
1School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Jilin 130117, China.
Insights
Ferroptosis, a cell death pathway, drives heart disease. Traditional Chinese Medicine (TCM) effectively combats ferroptosis in cardiomyocytes by targeting key pathways, offering new cardiovascular disease treatments.
Area of Science:
- Cardiovascular Research
- Cell Death Mechanisms
- Integrative Medicine
Background:
- Ferroptosis, an iron-dependent cell death, is implicated in various cardiomyopathies and myocardial injury.
- Dysregulation of the GPX4/System Xc- axis, iron, and lipid metabolism are central to ferroptosis in cardiovascular disease.
- Traditional Chinese Medicine (TCM) shows promise for cardioprotection by modulating ferroptosis.
Purpose of the Study:
- To review the molecular mechanisms of ferroptosis in cardiovascular diseases.
- To explore the cardioprotective effects of Traditional Chinese Medicine (TCM) interventions targeting ferroptosis.
- To highlight TCM's potential as a novel therapeutic strategy for cardiovascular diseases.
Main Methods:
- Comprehensive narrative review of recent literature on ferroptosis and cardiovascular disease.
- Systematic analysis of TCM active components, formulations, and therapies targeting ferroptosis pathways.
- Examination of evidence from diverse cardiovascular disease models.
Main Results:
- TCM interventions, including specific compounds and electroacupuncture, modulate ferroptosis-related pathways (Nrf2/HO-1/GPX4, p53/SLC7A11, PI3K/AKT).
- TCM alleviates cardiomyocyte ferroptosis by activating Nrf2, modulating iron, and inhibiting lipid peroxidation, improving cardiac function in disease models.
- TCM demonstrates synergistic multi-target, multi-pathway effects against ferroptosis.
Conclusions:
- Targeting ferroptosis presents a novel therapeutic avenue for cardiovascular diseases.
- TCM, with its complex mechanisms, holds significant potential for managing cardiovascular diseases by combating ferroptosis.
- Further research is needed to elucidate complex network mechanisms and advance clinical translation of TCM for cardiovascular disease.
Abstract:
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, playing a critical role in the pathogenesis of various cardiomyopathies, including hypertrophic, dilated, diabetic, ischemic, doxorubicin-induced, and septic cardiomyopathy, as well as myocardial ischemia-reperfusion injury. This article provides a comprehensive narrative review of the molecular mechanisms of ferroptosis-centered on dysregulation of the GPX4/System Xc- axis, iron metabolism, and lipid metabolism-and its role in cardiovascular diseases, with a specific focus on the cardioprotective effects of Traditional Chinese Medicine (TCM). Through a systematic analysis of recent literature, we highlight active components (e.g., baicalin, ginsenoside Rg3, resveratrol, tanshinone IIA), compound formulations (e.g., Qishen Granule, Zhilong Huoxue Tongyu Capsule), and electroacupuncture therapy, which exert effects via multi-target regulation of ferroptosis-related pathways such as Nrf2/HO-1/GPX4, p53/SLC7A11, and PI3K/AKT. Evidence indicates that TCM interventions effectively alleviate cardiomyocyte ferroptosis by activating the Nrf2 antioxidant pathway to upregulate GPX4/SLC7A11, modulating iron metabolism to reduce labile iron pools, and inhibiting ACSL4/ALOX15-mediated lipid peroxidation, with these effects validated in diverse cardiovascular disease models showing improved cardiac function. Targeting ferroptosis offers a novel therapeutic strategy for cardiovascular diseases, and TCM-with its synergistic multi-component, multi-target, multi-pathway advantages-holds significant potential in this context. Future research should prioritize elucidating complex network mechanisms and advancing clinical translation via high-quality studies to provide new theoretical foundations and drug candidates for cardiovascular disease management.