PANoptosis: a novel therapeutic target and mechanistic insight into traditional Chinese medicine intervention in inflammatory bowel disease: a review

Abstract

The rising incidence of inflammatory bowel disease (IBD) and the limited efficacy of current therapies underscore the need for novel strategies. PANoptosis is an inflammatory programmed cell-death process integrating molecular features of pyroptosis, apoptosis, and necroptosis. Emerging evidence suggests that PANoptosis-related genes and signaling nodes may contribute to intestinal epithelial injury, mucosal immune activation, barrier disruption, and inflammatory amplification in inflammatory bowel disease. Traditional Chinese medicine and its active constituents have been reported to regulate inflammation, intestinal barrier integrity, gut microbiota, and several cell-death pathways. However, direct evidence that these agents inhibit bona fide PANoptosis in intestinal models remains limited. Current mechanistic evidence is strongest for selected compounds, such as baicalin, which has been shown in macrophages to interfere with mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, whereas other proposed mechanisms are largely extrapolated from extra-intestinal models or from studies of apoptosis, pyroptosis, necroptosis, and inflammatory signaling. This narrative review summarizes the molecular basis of PANoptosis in IBD and critically evaluates the potential of traditional Chinese medicine-derived compounds and formulas to modulate upstream sensors, adaptor proteins, and downstream effectors of PANoptosis-related pathways. We emphasize that future studies should verify these mechanisms in intestinal epithelial cells, intestinal organoids, DSS/TNBS/IL-10-deficient colitis models, and human IBD tissues.