Application of natural products in regulating ferroptosis in human diseases

Ferroptosis is a type of cell death caused by excessive iron-induced peroxidation. It has been found to be involved in a variety of diseases, and natural products can be used to target ferroptosis in treatments. Natural products are biologically active compounds extracted or synthesized from nature. It is an important resource for the discovery of skeletons with a high degree of structural diversity and a wide range of bioactivities, which can be developed directly or used as a starting point for the optimization of new drugs. In this review, we aim to discuss the interactions between natural products and ferroptosis in the treatment of human diseases. Literature was searched in Pubmed, Science Direct, and Web of Science databases for the 11-year period from 2012 to 2023 using the search terms "natural products", "ferroptosis", "human disease", "neurodegenerative disease", "cardiovascular disease", and "cancer". In this research, the roles of natural products and ferroptosis were investigated. We suggest that natural products, such as terpenoids, flavonoids, polyphenols, alkaloids, and saponins, can be used in therapeutic applications for human diseases, as well as in ferroptosis. Additionally, the main mechanisms of ferroptosis were summarized and discussed. Furthermore, we propose that natural products can be utilized to enhance the sensitivity of cancer cells to ferroptosis, thus helping to overcome drug resistance and inhibit metastasis. Moreover, natural products have the potential to modulate the expression levels of ferroptosis-related factors. Finally, the future directions of this field were highlighted. The potential of natural products which focus on ferroptosis to treat human illnesses, particularly cancer, is very encouraging for human wellbeing.