2. Academic Validation
  3. A promising traditional Chinese medicine combination derived from Wuji Wan for gastric ulcer therapy by inhibiting ERS through targeting STAT3/PKR to promote autophagy signaling

A promising traditional Chinese medicine combination derived from Wuji Wan for gastric ulcer therapy by inhibiting ERS through targeting STAT3/PKR to promote autophagy signaling

  • Phytomedicine. 2026 Feb:151:157810. doi: 10.1016/j.phymed.2026.157810.
Wanfen Shu 1,  Guokun Zhang 1,  Tiantai Wu 2,  Jie Qian 1,  Qing Zhao 3,  Herong Li 1,  Chuang Zhang 1,  Xiaohuan Wang 1,  Yan Li 1,  Ziyu Li 1,  Xiuyue He 1,  Shuaishuai Chen 4,  Yang Jin 5,  Wen Liu 6
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guiyang 561113, China.
  • 2 First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, 550004, China.
  • 3 School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guiyang 561113, China; Clinical Trials Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550000, China.
  • 4 School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guiyang 561113, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guian New District, Guiyang 561113, China.
  • 5 School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guiyang 561113, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guian New District, Guiyang 561113, China. Electronic address: [email protected].
  • 6 School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guiyang 561113, China; School of Pharmaceutical Sciences, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
PMID: 41544468 DOI: 10.1016/j.phymed.2026.157810
Abstract

Background: Gastric ulcer (GU) remains clinically challenging due to high recurrence rates and adverse effects of conventional drugs. The classic traditional Chinese medicine (TCM) formula Wuji Wan (WJW) exhibited empirical efficacy in the treatment of GU. However, the precise mechanisms underlying the therapeutic effects of WJW's active ingredients remain unclear.

Purpose and methods: We developed a defined combination of eight bioactive WJW constituents (ComB) and investigated its anti-ulcer potential. In vitro, the cytoprotective effects of ComB were assessed in ethanol-injured GES-1 gastric epithelial cells. In vivo, rats with ethanol-induced GU were treated with ComB to evaluate mucosal repair. Mechanistic studies based on proteomics, target interaction studies, and cascade analysis of signaling pathways were conducted to dissect the mode of action of ComB.

Results: ComB showed significant protective effects, enhanced the viability of ethanol-injured GES-1 gastric epithelial cells, and reduced mucosal damage in the rat model of GU. Mechanistic studies revealed that ComB can directly bind to both STAT3 and PKR, effectively disrupting their molecular interaction and blocking the nuclear translocation of STAT3. This targeted intervention promoted autophagic flux and substantially alleviated endoplasmic reticulum stress (ERS) through coordinated regulation of the STAT3/PKR-autophagy signaling axis.

Conclusions: By directly disrupting the STAT3-PKR interaction, ComB inhibited STAT3 nuclear translocation, activated autophagic flux, and alleviated ERS, thereby protecting gastric mucosa against ethanol-induced damage. This study identified ComB as a promising traditional Chinese medicine combination for ethanol-induced GU therapy by inhibiting ERS through targeting STAT3/PKR to promote Autophagy signaling.

Keywords

Autophagy; Endoplasmic reticulum stress; Gastric ulcer; PKR; STAT3; Traditional Chinese Medicine; Wuji Wan.

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