PUBLICATION
Curcumin-mediated NRF2 induction limits inflammatory damage in, preclinical models of cystic fibrosis
- Authors
- Leon-Icaza, S.A., Frétaud, M., Cornélie, S., Bureau, C., Yatime, L., Floto, R.A., Renshaw, S.A., Herrmann, J.L., Langevin, C., Cougoule, C., Bernut, A.
- ID
- ZDB-PUB-250402-6
- Date
- 2025
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 186: 117957117957 (Journal)
- Registered Authors
- Langevin, Christelle, Renshaw, Steve A., Yatime, Laure
- Keywords
- Curcumin, Cystic fibrosis, Inflammation, NRF2, Oxidative response, Tissue repair, Zebrafish
- MeSH Terms
-
- Animals, Genetically Modified
- Animals
- Disease Models, Animal
- Neutrophils/drug effects
- Neutrophils/metabolism
- Reactive Oxygen Species/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Inflammation*/drug therapy
- Inflammation*/metabolism
- Inflammation*/pathology
- Humans
- Cystic Fibrosis*/drug therapy
- Cystic Fibrosis*/genetics
- Cystic Fibrosis*/metabolism
- Cystic Fibrosis*/pathology
- Curcumin*/pharmacology
- Cystic Fibrosis Transmembrane Conductance Regulator/genetics
- Cystic Fibrosis Transmembrane Conductance Regulator/metabolism
- NF-E2-Related Factor 2*/genetics
- NF-E2-Related Factor 2*/metabolism
- Zebrafish
- PubMed
- 40168724 Full text @ Biomed. Pharmacother.
Citation
Leon-Icaza, S.A., Frétaud, M., Cornélie, S., Bureau, C., Yatime, L., Floto, R.A., Renshaw, S.A., Herrmann, J.L., Langevin, C., Cougoule, C., Bernut, A. (2025) Curcumin-mediated NRF2 induction limits inflammatory damage in, preclinical models of cystic fibrosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 186:117957117957.
Abstract
Background Overactive neutrophilic inflammation causes damage to the airways and death in people with cystic fibrosis (CF), a genetic disorder resulting from mutations in the CFTR gene. Reducing the impact of inflammation is therefore a major concern in CF. Evidence indicates that dysfunctional NRF2 signaling in CF individuals may impair their ability to regulate their oxidative and inflammatory responses, although the role of NRF2 in neutrophil-dominated inflammation and tissue damage associated with CF has not been determined. Therefore, we examined whether curcumin, an activator of NRF2, might provide a beneficial effect in the context of CF.
Methods Combining Cftr-depleted zebrafish as an innovative biomedical model with CF patient-derived airway organoids (AOs), we aimed to understand how NRF2 dysfunction leads to abnormal inflammatory status and tissue remodeling and determine the effects of curcumin in reducing inflammation and tissue damage in CF.
Results We demonstrate that NFR2 is instrumental in regulating neutrophilic inflammation and repair processes in vivo, thereby preventing inflammatory damage. Importantly, curcumin treatment restores NRF2 activity in both CF zebrafish and AOs. Curcumin reduces neutrophilic inflammation in CF context, by rebalancing the production of epithelial ROS and pro-inflammatory cytokines. Furthermore, curcumin improves tissue repair by reducing CF-associated fibrosis. Our findings demonstrate that curcumin prevents CF-mediated inflammation via activating the NRF2 pathway.
Conclusions This work highlights the protective role of NRF2 in limiting inflammation and injury and show that therapeutic strategies to normalize NRF2 activity, using curcumin or others NRF2 activators, might simultaneously reduce airway inflammation and damage in CF.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping