Liquiritigenin regulates JAK/STAT3 and NF-κB signaling pathways to reduce colonic damage and barrier dysfunction caused by a high-salt diet.

Abstract

It has been shown that a high-salt diet (HSD) significantly damages the colonic epithelial barrier, resulting in increased intestinal permeability, upset gut microbial balance, and generalized inflammation. Despite this, effective therapeutic strategies to prevent HSD-induced intestinal damage remain limited. This study aims to explore the preventive properties and basic mechanisms of liquiritigenin (LG)，a natural flavonoid, against chronic colonic injury induced by prolonged HSD exposure. A murine model of chronic colitis was established by administering an 8 % NaCl diet, and LG therapy was used to evaluate how it affected the function of the intestinal barrier and allergic reactions. The development of pro- and anti-inflammatory cytokines (il-β, il-6, tnf-α, il-10, and inos) as well as important tight junction proteins (ZO-1, Claudin-3, and Occludin) was assessed. Furthermore, we investigated the molecular processes in vitro using normal colonic epithelial cell line NCM-460, with particular focus on the NF-κB and JAK/STAT3 signaling pathways. LG increased the expression of junction-binding proteins, greatly enhanced the intestinal wall integrity, and mitigated histopathological damage. Furthermore, it markedly attenuated excessive inflammatory responses both in vivo and in vitro. Mechanistically, LG suppressed the phosphorylation of key components within the pathways of JAK/STAT3 and NF-κB, thereby inhibiting downstream inflammatory signaling and epithelial cell injury. Collectively, these results demonstrate that liquiritigenin exerts protective effects against HSD-induced colonic damage by concurrently modulating the NF-κB and JAK/STAT3 pathways, highlighting its therapeutic potential for high salt-related intestinal disorders.