2. Academic Validation
  3. Palmatine ameliorates intestinal epithelial barrier injury in ulcerative colitis via targeting enolase 3

Palmatine ameliorates intestinal epithelial barrier injury in ulcerative colitis via targeting enolase 3

  • Int Immunopharmacol. 2025 Jun 20:162:115110. doi: 10.1016/j.intimp.2025.115110.
Yong Zhang 1,  Zixuan Lai 1,  Xiaoxia Hu 1,  Minghui Wu 1,  Shanshan Chen 2,  Linjie Su 2,  Shaoxia Xie 3,  Mihong Ren 1,  Bowen Yang 1,  Juan Wang 1,  Weimu Huang 1,  Ziren Su 4,  Zhuoming Li 5,  Youliang Xie 6
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China.
  • 2 Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, PR China.
  • 3 School of Medicine, South China University of Technology， Guangzhou, Guangdong, PR China.
  • 4 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, PR China.
  • 5 Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, PR China. Electronic address: lizhm5@mail.sysu.edu.cn.
  • 6 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, PR China.; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510120, PR China.. Electronic address: xieyl@gzucm.edu.cn.
PMID: 40543101 DOI: 10.1016/j.intimp.2025.115110
Abstract

Disruption of intestinal epithelial barrier is the major pathological characteristics of ulcerative colitis (UC). Palmatine (PAL) is a natural isoquinoline alkaloid derived from various traditional Chinese herbal medicines. The present study reported that PAL exerted anti-UC effects via protecting against intestinal epithelial cell injury and alleviating intestinal barrier dysfunction. In dextran sulfate sodium (DSS)-induced mice UC model, PAL alleviated symptoms like weight loss, diarrhea, rectal bleeding, colon shortening, and colon damage. In particular, PAL reduced intestinal permeability and FITC-dextran leakage, prevented the loss of goblet cells, increased expressions of mucins, tight junction (TJ) and adherens junction (AJ) proteins. In HCoEpiC cells, PAL promoted cell proliferation, inhibited Apoptosis, improved cell barrier function by reducing the penetration of FITC-dextran across the cell barrier and increasing transepithelial electrical resistance. By using the Cellular Thermal Shift Assay (CETSA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics technology, we identified Enolase 3 (ENO3) as the direct molecular target of PAL. CETSA, DARTS, and molecular docking confirmed PAL binds ENO3 and upregulates its expression. The protective effects of PAL on intestinal inflammation and barrier dysfunction were abolished when co-treated with ENOblock (an ENO3 inhibitor) or ENO3 knockdown by small interfering RNA, confirming that PAL alleviates UC by targeting ENO3. Mechanistically, Seahorse assays and ATP detection confirmed that PAL inhibits intestinal epithelial cell glycolysis to alleviate UC symptoms. In conclusion, our findings identify PAL as a novel phytochemical that displays anti-UC efficacy via targeting ENO3, endorsing its potential utility as a therapy for treatment of UC.

Keywords

Enolase 3; Intestinal barrier; Palmatine; Ulcerative colitis.

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