Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal inflammation with complex pathogenesis. Pyroptosis a pro-inflammatory programmed cell death mediated by gasdermin D (GSDMD) cleavage plays a pivotal role in disease progression through nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 classical and caspase-4/5/11 non-classical pathways. Targeting pyroptosis has emerged as a promising therapeutic strategy, with recent advances highlighting the potential of pyroptosis inhibitors such as small-molecule compounds, biologics, and repurposed drugs that specifically target NLRP3, caspases, or GSDMD to suppress inflammasome activation, block pore formation, and mitigate downstream inflammation. This review systematically summarizes the mechanisms and therapeutic effects of these inhibitors, while addressing critical challenges including drug specificity, delivery efficiency, and long-term safety, and explores their potential in combination therapies with existing IBD treatments to enhance clinical efficacy. By integrating preclinical and clinical evidence, we provide valuable insights into the translational prospects of pyroptosis-targeted therapies for precision management of IBD.