Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It is mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for the development of more effective UC therapies remains a pressing task for current research. Ferroptosis is a newly identified form of regulated cell death characterized by iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in the pathological processes of numerous diseases. A growing body of evidence suggests that the pathogenesis of UC is associated with ferroptosis, and the regulation of ferroptosis provides new opportunities for UC treatment. However, the specific mechanisms by which ferroptosis participates in the development of UC remain to be more fully and thoroughly investigated. Therefore, in this review, we focus on the research advances in the mechanism of ferroptosis in recent years and describe the potential role of ferroptosis in the pathogenesis of UC. In addition, we explore the underlying role of the crosslinked pathway between ferroptosis and other mechanisms such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, and gut microbiota in UC. Finally, we also summarize the potential compounds that may act as ferroptosis inhibitors in UC in the future.

Ulcerative colitis (UC) is an autoimmune disease with an incompletely understood pathogenesis. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway plays a key role in immune response and inflammation. More and more studies demonstrated that JAK/STAT signaling pathway is associated with the pathogenesis of UC. The JAK/STAT pathway affects UC in multiple ways by regulating intestinal inflammatory response, affecting intestinal mucosal barrier, modulating T cell homeostasis, and regulating macrophages. Encouragingly, natural products are promising candidates for the treatment of UC. Natural products have the advantage of being multi-targeted and rich in therapeutic modalities. This review summarized the research progress of JAK/STAT pathway-mediated UC. Furthermore, the latest studies on natural products targeting the JAK/STAT pathway for the treatment of UC were systematically summarized, including active ingredients such as arbutin, aloe polysaccharide, berberine, matrine, curcumin, Ginsenoside Rh2, and so on. The aim of this paper is to provide new ideas for drug development to regulate JAK/STAT signaling for treating UC.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized primarily by immune dysregulation. Its pathogenesis involves multiple factors, including dysregulation of T-cell subsets, hypersecretion of pro-inflammatory cytokines, imbalance in the gut microbiota, and disruption of the intestinal barrier. Among T-cell subsets, abnormal activation of Th1 and Th17 cells, in conjunction with Treg dysfunction, significantly amplifies local pro-inflammatory signals. Pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-17, exacerbate apoptosis and disrupt tight junctions (TJs) in intestinal epithelial cells (IECs), thereby creating favorable conditions for invasion by pathogenic bacteria and their metabolites. Intestinal microecological imbalance not only leads to significant alterations in the structure of the bacterial flora but also involves abnormal fluctuations in its metabolites that directly regulate intestinal immune homeostasis, a factor closely associated with the severity of inflammation and prognosis of ulcerative colitis. Recent studies have demonstrated that in the treatment of UC, traditional Chinese medicine (TCM) achieves a multi-target, multi-pathway integrated intervention by regulating immune cell differentiation, balancing inflammatory factor levels, repairing the intestinal epithelial barrier, and remodeling the structure of the bacterial flora. This article reviews the pathogenic mechanisms underlying immune dysregulation in UC and the advances in research on TCM’s role in immune regulation, anti-inflammatory repair, and flora modulation, encompassing the mechanisms of action of individual active ingredients and classic TCM compound formulas. Although some studies have preliminarily confirmed TCM’s potential to modulate immunity and repair the intestinal barrier, breakthroughs in mechanism analysis, herb standardization, and large-scale validation remain forthcoming. It is anticipated that the unique advantages of TCM will be translated into a more precise therapeutic strategy for UC through modern molecular and systems biology approaches.

Background: The incidence of inflammatory bowel disease (IBD) is rising worldwide, but epidemiological data on children and adolescents are lacking. Understanding the global burden of IBD among children and adolescents is essential for global standardization of methodology and treatment options. Methods: This is a cross-sectional study based on aggregated data. We estimated the prevalence and incidence of IBD in children and adolescents between 1990 and 2019 according to the Global Burden of Disease Study 2019 (GBD 2019). Age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were used to compare the burden and trends between different regions and countries. Results: In 2019, there were 25,659 new cases and 88,829 prevalent cases of IBD among children and adolescents globally, representing an increase of 22.8% and 18.5%, respectively, compared to 1990. Over the past 30 years, the incidence and prevalence of IBD among children and adolescents have been highest in high SDI regions, with the most significant increases in East Asia and high-income Asia Pacific. At the age level, incidence and prevalence were significantly higher in the 15–19-year-old age group, while the < 5-year-old group showed the most significant increase in incidence and prevalence. Conclusion: The incidence of IBD in children and adolescents is significantly on the rise in some countries and regions, and IBD will remain an important public health issue with extensive healthcare and economic costs in the future. The reported IBD burden in children and adolescents at the global, regional, and national levels will assist in the development of more precise health policies.

Ulcerative colitis (UC) is characterized by chronic non-recessive inflammation of the intestinal mucosa involving both innate and adaptive immune responses. Currently, new targeted therapies are urgently needed for UC, and neutrophil extracellular traps (NETs) are new therapeutic options. NETs are DNA-based networks released from neutrophils into the extracellular space after stimulation, in which a variety of granule proteins, proteolytic enzymes, antibacterial peptides, histones, and other network structures are embedded. With the deepening of the studies on NETs, their regulatory role in the development of autoimmune and autoinflammatory diseases has received extensive attention in recent years. Increasing evidence indicates that excess NETs exacerbate the inflammatory response in UC, disrupting the structure and function of the intestinal mucosal barrier and increasing the risk of thrombosis. Although NETs are usually assigned a deleterious role in promoting the pathological process of UC, they also appear to have a protective role in some models. Despite such progress, comprehensive reviews describing the therapeutic promise of NETs in UC remain limited. In this review, we discuss the latest evidence for the formation and degradation of NETs, focusing on their double-edged role in UC. Finally, the potential implications of NETs as therapeutic targets for UC will be discussed. This review aims to provide novel insights into the pathogenesis and therapeutic options for UC.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, the incidence of which continues to rise globally, and existing therapeutic options are limited by low drug bioavailability and systemic side effects. In this study, we systematically investigated the challenges of the special gastrointestinal environment of UC patients for oral drug delivery, such as extreme pH, degradation by digestive enzymes, metabolism of intestinal flora and obstruction of the intestinal mucosal barrier, and summarized the potential of plant-derived Exosome-like Nanovesicles (PELNs) as a novel delivery system. PELNs are produced by plant cells and mainly consist of proteins, RNA, lipids and plant active molecules. Animal and cell experiments have shown that they can treat UC through the regulation of the intestinal bacterial flora, the inhibition of inflammatory pathways, and the promotion of mucosal repair, etc. On the other hand, their small particle size (30– 500 nm), negative charge and lipid bilayer structure enable them to penetrate the intestinal mucus layer, tolerate extreme pH and enzymatic degradation, and adhere to intestinal epithelial cells through electrostatic interactions, thus possessing advantages such as low immunogenicity, high stability and natural targeting. Furthermore, the engineering modification of PELNs can significantly enhance targeting and therapeutic efficacy, such as surface modification or drug loading. Future research should focus on the systematic characterization, safety validation, large-scale production and multimodal combination therapy of PELNs in order to promote their clinical translation, which not only provides an efficient delivery platform for the treatment of UC, but also opens up a new pathway for the development of natural medicines.