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Updated: Feb 28, 2026
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An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance
Published on: December 3, 2020
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Shikonin improves intestinal barrier function through modulation of GPX4 expression in intestinal epithelial cells
Fuheng Yang1, Peihua Liang1, Hengli Guo2
1Department of Pharmacy, Zhuhai Women and Children's Hospital, Zhuhai, China.
International Journal of Immunopathology and Pharmacology
|February 26, 2026
Summary
Shikonin reduces ferroptosis in intestinal cells by increasing GPX4, enhancing CDX2 expression and barrier function. This mechanism, involving PKA/CREB signaling, suggests shikonin
Area of Science:
- Gastroenterology and Cell Biology
- Molecular Mechanisms of Disease
- Drug Discovery and Development
Background:
- Shikonin influences intestinal epithelial cell (IEC) differentiation via CDX2.
- Ferroptosis is implicated in IEC differentiation, but its role in shikonin's effects is unclear.
Purpose of the Study:
- To investigate the involvement of ferroptosis in shikonin-induced CDX2-mediated IEC differentiation.
Main Methods:
- Real-time PCR, Western blotting, luciferase assays, immunoprecipitation, and chromatin immunoprecipitation were employed.
- Experiments were conducted on HT-29 and Caco-2 cell lines.
Main Results:
- Shikonin treatment decreased ferroptosis by upregulating glutathione peroxidase 4 (GPX4) and solute carrier family 7 (cationic amino acid transporter) member 11.
- This led to enhanced CDX2 expression and improved IEC barrier function.
- Shikonin activated the PKA/CREB pathway, promoting CREB binding to the GPX4 promoter and GPX4 transactivation.
Conclusions:
- Shikonin inhibits ferroptosis via GPX4 upregulation, thereby promoting CDX2 expression and improving IEC barrier function.
- The PKA/CREB signaling pathway is crucial for shikonin's effects.
- Shikonin shows potential as a therapeutic agent for intestinal mucosal injury.
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