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.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel (IBD) disease characterized by a complex pathogenesis and limited treatment options. Macrophages play a key role in the pathophysiology of UC by regulating inflammatory responses and tissue repair processes. Currently, there is no comprehensive summary of macrophage regulatory pathways in UC, either domestically or internationally.Objective: This review aims to systematically elucidate the role of macrophages in UC and their specific regulatory mechanisms, and to identify potential therapeutic strategies and future research directions.Methods: A comprehensive literature review was conducted, integrating recent advances from global studies to explore macrophage-related pathways and functional alterations in UC. Special attention was given to studies investigating molecular mechanisms underlying macrophage polarization and function.Results: Evidence indicates that macrophage dysfunction is a central mechanism in the pathogenesis of UC. Major findings demonstrate that metabolic reprogramming serves as a fundamental pathway inducing phenotypic and functional alterations in macrophages. Additional mechanisms mediating these changes include epigenetic modifications, chemokine-driven recruitment, microbial metabolite induction, autophagy, and apoptosis. Multiple drugs targeting macrophages have shown effectiveness in treating UC.Conclusion: Targeting macrophage-related pathways represents an effective therapeutic approach for UC. This review provides a theoretical foundation for developing precision treatments focused on macrophage modulation and highlights important new avenues for future research.