Punicalagin alleviates enterotoxigenic Escherichia coli-induced intestinal mucosal injury via Krüppel-like factor 4

  • Chem Biol Interact. 2026 Jul 25:435:112182. doi: 10.1016/j.cbi.2026.112182.
Xiang-Guang Li  1 ,  Xiaowen Zhao  2 ,  Peizhi Zhu  3 ,  Jibin Fu  4 ,  Jiaxin Zhang  5 ,  Zhixin Yu  6 ,  Runting Chen  7 ,  Mingxia Chen  8 ,  Chuqiao Xiao  9 ,  Junxia Zheng  10
Affiliations
  • 1. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 2. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 3. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 4. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 5. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 6. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 7. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 8. College of Animal Science and Technology, Guangdong Polytechnic of Science and Trade, Qingyuan, 511500, China. Electronic address: [email protected].
  • 9. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
  • 10. Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address: [email protected].
PMID: 42219142 DOI: 10.1016/j.cbi.2026.112182
Abstract

Previous studies have shown that Enterotoxigenic Escherichia coli (ETEC) causes damage to the intestinal mucosal injury, and punicalagin (PUN) can help to ameliorate this damage. This study systematically investigates the protective effects of punicalagin on ETEC-induced intestinal damage and delineates the molecular targets implicated in its action. Experimental findings demonstrate that punicalagin administration significantly attenuates (P < 0.05) ETEC-induced weight loss, mucosal architecture disruption, and goblet cell depletion in a murine model. In parallel, punicalagin markedly enhances glycoprotein biosynthesis and cellular proliferation in ETEC-challenged IPEC-J2 cells (P < 0.05), concomitant with elevated expression levels of Krüppel-like factor 4 (KLF4), MUC2, Villin, ZO-1, and E-cadherin (P < 0.05). Mechanistic interrogation reveals that KLF4 overexpression robustly supports punicalagin-mediated restitution of glycoprotein synthesis and barrier-associated protein expression subsequent to ETEC insult, whereas KLF4 silencing compromises these restorative effects in IPEC-J2 cells. Collectively, these data position KLF4 as a pivotal regulator underpinning the beneficial effects of punicalagin on Mucin production and epithelial junctional integrity during ETEC Infection, thereby substantiating the mechanistic rationale for leveraging punicalagin as a targeted intervention in the management of ETEC-induced enteric disease.

Keywords
Enterotoxigenic Escherichia coli; Goblet cell; Intestinal injury; KLF4; Punicalagin.
Products