2. Academic Validation
  3. Isodeoxyelephantopin mitigates DSS-induced ulcerative colitis by suppressing IL-1β-driven inflammation via the TXNIP/NLRP3 axis

Isodeoxyelephantopin mitigates DSS-induced ulcerative colitis by suppressing IL-1β-driven inflammation via the TXNIP/NLRP3 axis

  • Phytomedicine. 2026 Jan 16:153:157839. doi: 10.1016/j.phymed.2026.157839.
Li-Yuan Lin 1,  Heng-Zhen Li 2,  Xiang-Qian Liu 3,  Si Xiong 2,  Man-Mei Li 4,  He-Yun Zhang 5,  Chui-Wen Qian 6,  Zhong Liu 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Molecules and Druggability Assessment & College of Pharmacy, Jinan University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
  • 2 School of Pharmacy, Jinan University, Guangzhou, China.
  • 3 Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
  • 4 State Key Laboratory of Bioactive Molecules and Druggability Assessment & College of Pharmacy, Jinan University, Guangzhou, China; School of Pharmacy, Jinan University, Guangzhou, China.
  • 5 Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: [email protected].
  • 6 Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 7 Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China; State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macau, China. Electronic address: [email protected].
PMID: 41655542 DOI: 10.1016/j.phymed.2026.157839
Abstract

Background: Isodeoxyelephantopin (IDET) is a sesquiterpene lactone isolated from traditional herb Elephantopus scaber, which is known for its anti-inflammatory activities. While our previous study demonstrated that IDET inhibits NLRP3 expression in an acute peritonitis model, its therapeutic potential in chronic inflammatory diseases such as ulcerative colitis (UC), as well as the underlying mechanisms involving inflammasome signaling, have not yet been fully elucidated.

Purpose: This research was designed to explain the protective capacity of IDET in UC and to clarify how IDET modulates IL-1β-mediated inflammatory responses through the TXNIP/NLRP3 signaling pathway, by integrating in vitro and in vivo experimental systems.

Results: IDET significantly reduced dextran sulfate sodium (DSS)-induced colitis in mice, improving disease scores, reducing inflammation, and preserving colon histology. Mechanistically, IDET exerted a multi-tiered suppression of the inflammasome pathway, which suppresses IL-1β-driven inflammation. Firstly, it disrupted the upstream priming signal by downregulating NLRP3 expression through NF-κB signaling pathway. Secondly, it inhibited inflammasome assembly, as evidenced by reduced ASC oligomerization and NLRP3-ASC interaction. Consequently, IDET reduced the cleavage of pro-caspase-1 and pro-IL-1β, resulting in an approximately 4-fold reduction in mature IL-1β secretion. A key finding was that IDET interfered with the activation signal by attenuating the TXNIP-NLRP3 interaction, according to immunoprecipitation and molecular docking results.

Conclusions: Extending our previous findings on its anti-acute inflammatory activity, this study demonstrates that IDET alleviates experimental ulcerative colitis by targeting multiple stages of NLRP3 inflammasome activation. The results highlight the translational potential of IDET, a natural compound, for treating chronic intestinal inflammation.

Keywords

IL-1β; Inflammasome; Isodeoxyelephantopin; TXNIP; Ulcerative colitis.

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