Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation of ferrous ions (Fe²⁺) and lipid peroxides. As the metabolic hub of the body, the liver is crucial for iron storage and lipid metabolism. The liver seems to be closely related to ferroptosis through iron and lipid metabolism. Liver disease greatly threatens host health, and exploring effective interventions is essential. Mounting studies have demonstrated that ferroptosis is one of the possible pathogenic mechanisms involved in liver disease. Targeting ferroptosis may provide a promising opportunity for treating liver disease. However, drugs targeting ferroptosis are extremely limited. Therefore, it is an urgent need to develop new and safe ferroptosis regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, have recently shown great therapeutic potential in liver disease via modulating ferroptosis-related genes or pathways. Here, we outline the molecular mechanism of ferroptosis and systematically summarize the regulatory function of NAC on ferroptosis in liver disease. Finally, we discuss the application prospects and potential problems concerning NAC as ferroptosis regulators for managing liver disease.