Progress in the Treatment of Ulcerative Colitis by Targeting NLRP3 Inflammasome

Ulcerative colitis (UC) is a chronic inflammatory disease occurred in intestinal tract, characterized by a prolonged treatment course and associated with severe complications, exerting significant negative impacts on patients' quality of life. In recent years, the incidence of UC has been increasing. Consequently, identifying novel therapeutic targets and innovative drugs is of paramount importance for UC treatment. The aberrant activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome exacerbates intestinal mucosal damage through releasing inflammatory cytokines. Thus, targeting NLRP3 inflammasome to inhibit its activation has emerged as a breakthrough strategy for UC therapy. Small molecule compounds can apply inhibitory effects by binding to NLRP3-associated domains and modulating the activation phase. In this review, we describe the mechanism of NLRP3 inflammasome and systematically summarizes compounds targeting different domains of NLRP3 inflammasome, along with their core structures. Furthermore, candidate compounds and those validated in Nlrp3-knockout (Nlrp3 ^-/-) models will also be discussed, which provides innovative methods and new insights for precision treatment of UC.