Protective Effects of Herbacetin in Experimental Colitis: Targeting NF-κB and NLRP3 Pathways.

Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) resulting from a dysregulation of immune responses. Herbacetin, a flavonoid of natural origin, has been found to exert an anti-inflammatory action, though its actions in experimental colitis are unknown. Colitis was induced in BALB/c mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Mice were administered with herbacetin (25, 50, 100&#x2009;mg/kg) or sulfasalazine (100&#x2009;mg/kg) orally for 7 days. The disease activity index (DAI), colon length, weight/length ratio, histopathology, MPO and NO contents, and inflammatory gene expression (NF-&#x3ba;B, iNOS, COX-2, NLRP3, IL-1&#x3b2;, IL-18) were evaluated. TNBS induced marked&#x2002;weight loss and increased DAI (p&#x2009;<&#x2009;0.01 vs. NC). Body weight (p&#x2009;<&#x2009;0.01) and DAI (p&#x2009;<&#x2009;0.01) were significantly ameliorated by herbacetin, especially at 50 and 100&#x2009;mg/kg. TNBS significantly reduced the colon length (p&#x2009;<&#x2009;0.001) and increased the weight/length ratio (p&#x2009;<&#x2009;0.001), which were significantly counteracted by&#x2002;herbacetin (p&#x2009;<&#x2009;0.01-0.001). TNBS mice presented with mucosal injury and inflammatory infiltration were demonstrated&#x2002;by histopathology (p&#x2009;<&#x2009;0.001) and a dose-dependent healing effect was observed in herbacetin-treated mice. TNBS mice had higher levels&#x2002;of MPO and NO (p&#x2009;<&#x2009;0.001), which were significantly attenuated by herbacetin (p&#x2009;<&#x2009;0.01-0.001). Herbacetin decreased the mRNA expression&#x2002;levels of NF-&#x3ba;B, iNOS, COX-2, NLRP3, IL-1&#x3b2;, and IL-18 in a dose-dependent (p&#x2009;<&#x2009;0.05-0.001). Herbacetin exerts a protective effect in colitis by suppressing neutrophil infiltration, oxidative stress, and NF-&#x3ba;B-NLRP3-mediated inflammation, highlighting the potential of herbacetin-based treatment for UC and related inflammatory bowel diseases.