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Updated: Apr 19, 2026
Author Spotlight: Understanding Cytokine-Induced Cell Death in Intestinal Epithelial Cells Using Human Organoids
Published on: August 2, 2024
Organoid phenotypic screening identified glycyrrhizin that confers protection against tumor necrosis factor-induced
Yu Takahashi1, Zhongwei Zhang2, Izumi Tanaka2
1Food Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Abstract:
Human organoids are considered physiological models that reflect human physiology; however, their applications in drug screening studies are limited. To develop a fundamental treatment for recurrent Crohn's disease (CD), in which tumor necrosis factor (TNF) is a key pathogenic factor, we conducted phenotypic drug screening to prevent TNF-induced cell death in human intestinal epithelial organoids. Glycyrrhizin, a natural product of licorice root, dose-dependently blocked TNF-induced cell death in organoids but not in TNF-sensitive L929 cells; L929 cells exhibited necroptosis, whereas organoid-derived cells preferentially showed apoptosis upon TNF treatment, determining the specificity of glycyrrhizin. Glycyrrhizin inhibited downstream caspase-8 signaling, which is essential for TNF-dependent apoptosis, and ameliorated intestinal inflammation in vivo. These results demonstrate that glycyrrhizin may be a novel therapeutic compound for CD and highlight the importance of using organoids for phenotypic drug screening.
Insights
Glycyrrhizin, derived from licorice root, shows potential as a Crohn
Area of Science:
- Biomedical Research
- Drug Discovery
- Gastroenterology
Background:
- Human organoids offer physiological relevance but have limited drug screening applications.
- Tumor necrosis factor (TNF) is a critical factor in the pathogenesis of Crohn's disease (CD).
Purpose of the Study:
- To identify therapeutic compounds for Crohn's disease using organoid-based phenotypic drug screening.
- To investigate the mechanism of action of potential drug candidates in preventing TNF-induced cell death.
Main Methods:
- Phenotypic drug screening was performed on human intestinal epithelial organoids.
- TNF-induced cell death pathways (apoptosis and necroptosis) were analyzed.
- The effect of glycyrrhizin on inflammatory markers in vivo was assessed.
Main Results:
- Glycyrrhizin effectively blocked TNF-induced cell death in organoids in a dose-dependent manner.
- Glycyrrhizin demonstrated specificity, inhibiting apoptosis in organoid cells but not necroptosis in L929 cells.
- Glycyrrhizin suppressed caspase-8 signaling and reduced intestinal inflammation in vivo.
Conclusions:
- Glycyrrhizin emerges as a potential therapeutic agent for Crohn's disease.
- Organoid models are valuable for phenotypic drug screening and disease mechanism studies.
