Vitamin D3 in synergy with triple therapy to eradicate Helicobacter pylori infection in mice via the c-Raf/MEK/ERK pathway

  • Tissue Cell. 2026 Oct:102:103551. doi: 10.1016/j.tice.2026.103551.
Shuai Zhao  1 ,  Chengyan Shan  1 ,  Yaoyao Zhong  2 ,  Daihong Wan  1 ,  Yi Xin  3 ,  Wenxiao Wang  4
Affiliations
  • 1. Pediatric Department of Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, China.
  • 2. Pediatric Department of Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong 266011, China.
  • 3. Pediatric Department of Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, China. Electronic address: [email protected].
  • 4. Pediatric Department of Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, China. Electronic address: [email protected].
PMID: 42033901 DOI: 10.1016/j.tice.2026.103551
Abstract

Background: Helicobacter pylori (H. pylori) is a primary pathogen associated with gastritis, peptic ulcers, and gastric Cancer. Current eradication therapies are increasingly compromised by Antibiotic resistance. Vitamin D3 (VD3) has shown potential as an adjunct therapy, yet its underlying mechanism remains unclear.

Objective: This study evaluated the efficacy of VD3 combined with triple therapy on H. pylori eradication in mice, assessing pathological changes, Infection and inflammation levels and epithelial cell death; furthermore, it explored the mechanism of the synergistic effect.

Methods: An in vivo model was inoculated with H. pylori to establish in mice. After four weeks, mice were treated with VD3, triple therapy, quadruple therapy (omeprazole, amoxicillin, clarithromycin and bismuth potassium citrate), or their combinations for another four weeks. Hematoxylin and Eosin (H&E) staining, quantitative Real-Time PCR, colony formation, immunoblotting, enzyme-linked immunosorbent assay (ELISA), TUNEL staining, and Caspase activity assays were used to evaluate the effect of VD3.

Results: Compared to triple therapy alone, the combination of VD3 and triple therapy reduced gastritis severity, H. pylori 16S rDNA expression, and Bacterial colony counts in infected mice. It also decreased mRNA and protein levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, reduced gastric epithelial cell Apoptosis, and suppressed Caspase-3/6/9 activities. VD3 treatment further enhanced C-Raf, MEK, and ERK phosphorylation in gastric tissues. Importantly, the ERK Inhibitor U0126 abrogated the therapeutic benefits of VD3 combined with triple therapy, leading to increased gastritis severity, H. pylori 16S rDNA expression, Bacterial colony counts, and Caspase activity.

Conclusion: Vitamin D3 synergizes with triple therapy to eradicate H. pylori Infection by exhibiting Antibacterial, anti-inflammatory, and cytoprotective effects through regulation of the C-Raf/MEK/ERK signaling pathway.

Keywords
C-Raf/MEK/ERK Pathway; Helicobacter pylori; Triple Therapy; Vitamin D(3).
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