Inhibition of ferroptosis: A new direction in the treatment of ulcerative colitis by traditional Chinese medicine

Ulcerative colitis (UC) is a chronic idiopathic intestinal disease of unknown cause and has been classified as one of the modern intractable diseases by the World Health Organization (WHO). Ferroptosis, as an iron-ion-dependent mode of programmed cell death, is closely related to iron metabolism, lipid peroxidation, and imbalance of the antioxidant system, and plays an important role in the development of UC. In this paper, we will review the regulatory pathways of ferroptosis, the relationship between ferroptosis and the pathogenesis of UC, and the treatment of UC by TCM from the perspective of ferroptosis inhibition, and summarize the mechanism of action of the active ingredients of TCM and TCM compounds to improve UC through ferroptosis inhibition, and look forward to the prospect of the application of ferroptosis inhibition by TCM in the treatment of UC. This paper aims to elucidate the mechanism of action of TCM active ingredients and TCM combinations in the treatment of UC by inhibiting ferroptosis. The active ingredients of TCM have the significant advantages of multi-targets and multi-pathways, and ferroptosis is the current research hotspot in the prevention and treatment of UC, so the inhibition of ferroptosis by TCM is a key direction for future research. The keywords "ferroptosis", "ulcerative colitis" and "TCM" were searched in Pubmed, CNKI, and Wed of Science databases. Papers related to clinical trials and pharmacological research up to August 2023 were screened for inclusion. Combined with the theory of TCM, we systematically summarized the effects of TCM active ingredients and TCM combinations in inhibiting ferroptosis and thus preventing UC. A large number of studies have shown that TCM active ingredients and TCM combinations inhibit the inflammatory response and oxidative stress in the course of UC mainly by interfering with iron metabolism, correcting lipid metabolism and peroxidative accumulation, and regulating the processes of glutathione (GSH) and glutathione peroxidase 4 (GPX4), to improve colonic mucosal damage and promote the repair of colonic mucosal tissue. Since the study of ferroptosis in UC is still in the exploratory stage, many issues still deserve attention in the future. This paper reviews the mechanism of ferroptosis inhibition by TCM active ingredients and TCM combinations to prevent and treat UC. In the future, we should also further increase the number of clinical experimental studies to explore whether more TCM medicines can play a therapeutic role in UC by inhibiting ferroptosis, and explore more pathways and genes targeting the inhibition of ferroptosis, to seek more TCM therapies for UC. We believe that the use of TCM active ingredients and TCM combinations to regulate ferroptosis is an important direction for future UC prevention and treatment.