Regulatory mechanisms and therapeutic targets of programmed cell death in intestinal epithelial cells in inflammatory bowel disease.

Abnormal activation of programmed cell death (PCD) in intestinal epithelial cells (IECs) is a key driving force for intestinal barrier destruction and the vicious cycle of inflammation in inflammatory bowel disease (IBD). In recent years, the death modes in IECs in IBD have expanded from apoptosis to the synergistic involvement of multiple PCD pathways such as necroptosis, pyroptosis, ferroptosis, and PANoptosis. This review summarizes the molecular features of these death modalities and their pathological significance in IBD, focusing on the multi-level regulatory mechanisms, from molecular and cellular interactions to tissue microenvironment and system integration. It discusses the intervention strategies targeting the death pathways and the application potential of natural products and traditional Chinese medicine compounds. Given the current challenges, such as mechanism heterogeneity, we propose future research directions that warrant further investigation, aiming to provide a theoretical basis for the precise regulation of PCD in IECs in IBD and the discovery of therapeutic targets.