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

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

  • Mol Immunol. 2026 Feb:190:86-100. doi: 10.1016/j.molimm.2026.01.005.
Weiping Yan 1,  Lei Wang 2,  Wenting Zhu 1,  Xiao Liu 1,  Zihan Xu 1,  Juntong Liu 1,  Jie Ding 1,  Mengling Zhu 1,  Fenfen Ma 3,  Zibo Dong 4
Affiliations

Affiliations

  • 1 Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
  • 2 Department of Laboratory Medicine, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222000, China.
  • 3 Department of Cardiac Function Examination, The Second People's Hospital of Lianyungang City, Lianyungang Second People's Hospital Affiliated to Kangda College of Nanjing Medical University, Lianyungang Clinical College, Bengbu Medical College, Lianyungang Clinical College of Nantong University, Lianyungang 222006, China. Electronic address: [email protected].
  • 4 Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China. Electronic address: [email protected].
PMID: 41558083 DOI: 10.1016/j.molimm.2026.01.005
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.

Keywords

Colitis; High-salt diet; Intestinal barrier; JAK/STAT3; Liquiritigenin; NF-κB.

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