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Published on: January 5, 2017

TNFAIP1 as a novel therapeutic target in ulcerative colitis and salidroside as its potential inhibitor

Qi Ouyang1, Shengye Tian1, Hong Jiang1

  • 1The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|July 14, 2026
PubMed
Abstract

Insights

Researchers identified TNFAIP1 as a key driver of ulcerative colitis (UC). They discovered Salidroside, a natural compound, directly targets TNFAIP1, showing therapeutic potential for UC treatment.

Area of Science:

  • Gastroenterology
  • Immunology
  • Pharmacology

Background:

  • Tumor Necrosis Factor Alpha Induced Protein 1 (TNFAIP1) lacks known inhibitors, hindering its therapeutic exploration for ulcerative colitis (UC).
  • TNFAIP1's role in UC pathogenesis remained largely uncharacterized, limiting targeted treatment strategies.

Purpose of the Study:

  • To validate TNFAIP1 as a pathogenic factor in ulcerative colitis.
  • To identify the first direct TNFAIP1-targeting therapeutic compound derived from natural sources.

Main Methods:

  • Integrated bioinformatics, DSS-induced colitis mouse models, and virtual screening to identify TNFAIP1 inhibitors.
  • Utilized cellular thermal shift and ubiquitination assays to confirm Salidroside's direct interaction with TNFAIP1.
  • Assessed Salidroside's efficacy in ameliorating colitis in wild-type mice.

Main Results:

  • TNFAIP1 expression was significantly elevated in UC patients and colitic mice.
  • TNFAIP1 knockout mice exhibited resistance to colitis, linked to suppressed inflammatory pathways (IKK/IκB/NF-κB, CREB) and improved gut microbiota.
  • Salidroside, identified via virtual screening, directly bound TNFAIP1, phenocopied genetic knockout effects, reduced colitis severity, and downregulated TNFAIP1-driven inflammation.

Conclusions:

  • TNFAIP1 is confirmed as a critical pathogenic driver in ulcerative colitis.
  • Salidroside emerges as a novel, first-in-class direct TNFAIP1 inhibitor with significant therapeutic potential for UC.
Keywords:
Gut microbiotaSalidrosideTNFAIP1UC

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