Dysregulated programmed cell death of intestinal epithelial cells in ulcerative colitis: Molecular mechanisms and novel therapeutic interventions (Review).

Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disease affecting the colonic mucosa, has seen a rising global incidence and poses a growing public health challenge. The clinical presentation typically includes recurrent abdominal pain, hematochezia, weight loss and structural damage to the colonic epithelium, substantially impacting patients' quality of life. Recent research has underscored the role of intestinal barrier dysfunction as a fundamental driver of persistent inflammation and disease progression in UC. Intestinal epithelial cells (IECs) form a monolayer through tight intercellular junctions and constitute the primary defense against luminal pathogens. Dysregulation of programmed cell death pathways in IECs such as apoptosis, necroptosis, pyroptosis, ferroptosis and autophagy‑related cell death compromises epithelial integrity and exacerbates inflammation. The present review systematically examines how these death pathways contribute to UC pathogenesis, highlighting the molecular mechanisms through which natural bioactive compounds and nanoparticle‑based drug delivery systems modulate them. Key signaling targets include the NF‑κB pathway, MAPK cascade, NLR family pyrin domain containing 3 inflammasome and autophagy‑related networks. By integrating advances in target identification, structure‑activity relationship optimization and mechanistic insights, the present review provides a comprehensive framework for understanding UC and facilitates the development of innovative therapeutic approaches aimed at restoring barrier function and regulating epithelial cell death.