Natural products and ferroptosis: A novel approach for heart failure management

BACKGROUND: The discovery of ferroptosis has brought a revolutionary breakthrough in heart failure treatment, and natural products, as a significant source of drug discovery, are gradually demonstrating their extraordinary potential in regulating ferroptosis and alleviating heart failure symptoms. In addition to chemically synthesized small molecule compounds, natural products have attracted attention as an important source for discovering compounds that target ferroptosis in treating heart failure. PURPOSE: Systematically summarize and analyze the research progress on improving heart failure through natural products' modulation of the ferroptosis pathway. METHODS: By comprehensively searching authoritative databases like PubMed, Web of Science, and China National Knowledge Infrastructure with keywords such as "heart failure", "cardiovascular disease", "heart disease", "ferroptosis", "natural products", "active compounds", "traditional Chinese medicine formulas", "traditional Chinese medicine", and "acupuncture", we aim to systematically review the mechanism of ferroptosis and its link with heart failure. We also want to explore natural small-molecule compounds, traditional Chinese medicine formulas, and acupuncture therapies that can inhibit ferroptosis to improve heart failure. RESULTS: In this review, we not only trace the evolution of the concept of ferroptosis and clearly distinguish it from other forms of cell death but also establish a comprehensive theoretical framework encompassing core mechanisms such as iron overload and system xc-/GSH/GPX4 imbalance, along with multiple auxiliary pathways. On this basis, we innovatively link ferroptosis with various types of heart failure, covering classic heart failure types and extending our research to pre-heart failure conditions such as arrhythmia and aortic aneurysm, providing new insights for early intervention in heart failure. Importantly, this article systematically integrates multiple strategies of natural products for interfering with ferroptosis, ranging from monomeric compounds and bioactive components to crude extracts and further to traditional Chinese medicine formulae. In addition, non-pharmacological means such as acupuncture are also included. CONCLUSION: This study fills the gap in the systematic description of the relationship between ferroptosis and heart failure and the therapeutic strategies of natural products, aiming to provide patients with more diverse treatment options and promote the development of the heart failure treatment field.