Ferroptosis-Modulating Natural Products for Targeting Inflammation-Related Diseases: Challenges and Opportunities in...

Significance: Numerous disorders are linked to ferroptosis, a form of programmed cell death triggered by lipid peroxidation accumulation rather than apoptosis. Inflammation is the body's defensive response to stimuli and is also caused by inflammatory chemicals that can harm the body. The treatment of inflammatory diseases by focusing on the signaling pathways and mechanisms of ferroptosis has emerged as a new area worthy of extensive research. Recent Advances: Studies in cellular and animal models of inflammatory diseases have shown that ferroptosis markers are activated and lipid peroxidation levels are increased. Natural products (NPs) are gaining importance due to their ability to target ferroptosis pathways, particularly the Nuclear factor E2-related factor 2 signaling pathway, thereby suppressing inflammation and the release of pro-inflammatory cytokines. Critical Issues: This article provides an overview of ferroptosis, focusing on the signaling pathways and mechanisms connecting it to inflammation. It also explores the potential use of NPs as a treatment for inflammatory diseases and ferroptosis. Future Directions: NPs offer unique advantages, including multicomponent properties, multi-bio-targeting capabilities, and minimal side effects. Further research may facilitate the early clinical application of NPs to develop innovative treatment strategies. Antioxid. Redox Signal. 41, 976-991.