Natural products protect against spinal cord injury by inhibiting ferroptosis: a literature review

Spinal cord injury (SCI) is a severe traumatic condition that frequently results in various neurological disabilities, including significant sensory, motor, and autonomic dysfunctions. Ferroptosis, a recently identified non-apoptotic form of cell death, is characterized by the accumulation of reactive oxygen species (ROS), intracellular iron overload, and lipid peroxidation, ultimately culminating in cell death. Recent studies have demonstrated that ferroptosis plays a critical role in the pathophysiology of SCI, contributing significantly to neural cell demise. Three key cellular enzymatic antioxidants such as glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and dihydroorotate dehydrogenase (DHODH), have been elucidated as crucial components in the defense against ferroptosis. Natural products, which are bioactive compounds mostly derived from plants, have garnered considerable attention for their potential therapeutic effects. Numerous studies have reported that several natural products can effectively mitigate neural cell death and alleviate SCI symptoms. This review summarizes fifteen natural products containing (−)-Epigallocatechin-3-gallate (EGCG), Proanthocyanidin, Carnosic acid, Astragaloside IV, Trehalose, 8-gingerol, Quercetin, Resveratrol, Albiflorin, Alpha-tocopherol, Celastrol, Hispolon, Dendrobium Nobile Polysaccharide, Silibinin, and Tetramethylpyrazine that have shown promise in treating SCI by inhibiting ferroptosis. Additionally, this review provides an overview of the mechanisms involved in these studies and proposes several perspectives to guide future research directions.