Nature-Inspired Bioactive Compounds: A Promising Approach for Ferroptosis-Linked Human Diseases?

Ferroptosis is a type of cell death driven by iron overload and lipid peroxidation. It is considered a key mechanism in the development of various diseases such as atherosclerosis, Alzheimer, diabetes, cancer, and renal failure. The redox status of cells, such as the balance between intracellular oxidants (lipid peroxides, reactive oxygen species, free iron ions) and antioxidants (glutathione, glutathione Peroxidase 4), plays a major role in ferroptosis regulation and constitutes its principal biomarkers. Therefore, the induction and inhibition of ferroptosis are promising strategies for disease treatments such as cancer or neurodegenerative and cardiovascular diseases, respectively. Many drugs have been developed to exert ferroptosis-inducing and/or inhibiting reactions, such as erastin and iron-chelating compounds, respectively. In addition, many natural bioactive compounds have significantly contributed to regulating ferroptosis and ferroptosis-induced oxidative stress. Natural bioactive compounds are largely abundant in food and plants and have been for a long time, inspiring the development of various low-toxic therapeutic drugs. Currently, functional bioactive peptides are widely reported for their antioxidant properties and application in human disease treatment. The scientific evidence from biochemical and in vitro tests of these peptides strongly supports the existence of a relationship between their antioxidant properties (such as iron chelation) and ferroptosis regulation. In this review, we answer questions concerning ferroptosis milestones, its importance in physiopathology mechanisms, and its downstream regulatory mechanisms. We also address ferroptosis regulatory natural compounds as well as provide promising thoughts about bioactive peptides.