Curcumin, the primary bioactive substance in turmeric, exhibits potential therapeutic effects on ulcerative colitis. However, its mechanism for regulating necroptosis in colitis has not been fully elucidated. In this study, the effect of curcumin on experimental colitis-induced necroptosis of intestinal epithelial cells was investigated, and its molecular mechanism was further explored. We found that curcumin blocked necroptosis in a dose-dependent manner by inhibiting the phosphorylation of RIP3 and MLKL instead of RIP1 in HT-29 cells. Co-Immunoprecipitation assay showed that curcumin weakened the interaction between RIP1 and RIP3, possibly due to the direct binding of curcumin to RIP3 as suggested by drug affinity responsive target stability analysis. In a classical model of TNF-α and pan-caspase inhibitor-induced necroptosis in C57BL/6 mice, curcumin potently inhibited systemic inflammatory responses initiated by the necroptosis signaling pathway. Then, using a dextran sodium sulfate-induced colitis model in C57BL/6 mice, we found that curcumin inhibited the expression of p-RIP3 in the intestinal epithelium, reduced intestinal epithelial cells loss, improved the function of the intestinal tight junction barrier, and reduced local intestinal inflammation. Collectively, our findings suggest that curcumin is a potent targeted RIP3 inhibitor with anti-necroptotic and anti-inflammatory effects, maintains intestinal barrier function, and effectively alleviates colitis injury.
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http://dx.doi.org/10.3389/fphar.2023.1170637 | DOI Listing |
Int J Biol Sci
January 2025
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
PIEZO1 has been found to play a vital role in regulating intestinal epithelial cells (IEC) function and maintaining intestinal barrier in recent years. Therefore, IEC PIEZO1 might exert a significant impact on liver metabolism through the gut-liver axis, but there is no research on this topic currently. Classic high-fat diet (HFD) model and mice with IEC-specific deficiency of PIEZO1 ( ) were used to explore the problem.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
Plasticity is needed during development and homeostasis to generate diverse cell types from stem and progenitor cells. Following differentiation, plasticity must be restricted in specialized cells to maintain tissue integrity and function. For this reason, specialized cell identity is stable under homeostatic conditions; however, cells in some tissues regain plasticity during injury-induced regeneration.
View Article and Find Full Text PDFNat Metab
January 2025
Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Transmembrane-6 superfamily member 2 (TM6SF2) regulates hepatic fat metabolism and is associated with metabolic dysfunction-associated steatohepatitis (MASH). TM6SF2 genetic variants are associated with steatotic liver disease. The pathogenesis of MASH involves genetic factors and gut microbiota alteration, yet the role of host-microbe interactions in MASH development remains unclear.
View Article and Find Full Text PDFFood Chem Toxicol
January 2025
Department of Food Biotechnology and Microbiology, Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC-UAM), Nicolás Cabrera 9, 28049 Madrid, Spain. Electronic address:
The consumption of dietary emulsifiers, including polysorbate 80 (P80) and sodium carboxymethylcellulose (CMC), has raised safety concerns due to its interaction with the intestinal microbiome. This study demonstrated that increasing concentrations of P80 and CMC added to a dynamic four-stage gut microbiota model (BFBL gut simulator) altered the microbiome composition and impacted epithelial integrity in a dose-dependent manner. 16S rDNA amplicon-based metagenomics analysis revealed that these emulsifiers increased microbial groups with proinflammatory capacities while decreasing microbial taxa known to enhance barrier function.
View Article and Find Full Text PDFActa Histochem Cytochem
December 2024
Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807-8555, Japan.
Inflammatory bowel disease is triggered by abnormalities in epithelial barrier function and immunological responses, although its pathogenesis is poorly understood. The dextran sodium sulphate (DSS)-induced colitis model has been used to examine inflammation in the colon. Damage to mucosa primality occurs in the large intestine and scarcely in the small intestine.
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