| RRC ID |
87826
|
| Author |
Takahashi Y, Zhang Z, Tanaka I, Lee IT, He J, Koura Y, Sato S, Kojima H, Okabe T, Kiyono H, Sasaki T, Yamauchi Y, Kurashima Y, Sato R.
|
| Title |
Organoid phenotypic screening identified glycyrrhizin that confers protection against tumor necrosis factor-induced cell death.
|
| Journal |
Stem Cell Reports
|
| 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.
|
| Pages |
102891
|
| Published |
2026-4-16
|
| DOI |
10.1016/j.stemcr.2026.102891
|
| PII |
S2213-6711(26)00102-5
|
| PMID |
41997150
|
| Resource |
| DNA material |
CSII-EF-MCS-IRES2-Venus (RDB04384) |
