ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Predictive Toxicology
This article is part of the Research TopicUsing Organoids and Organ Chips as tools to test the safety in developing Natural Medicinal Substances and Novel FoodView all articles
The dietary phytochemicals carnosic acid and sulforaphane regulate inflammatory markers in ulcerative colitis patient-derived colonoids
Provisionally accepted
Rocío Rivera Rodríguez1Siri Sæterstad2Ann-Therese Chattergoon Ali2Linn-Karina M. Selvik2
Ingunn Bakke2
Torunn Bruland2
Jeremy James Johnson1*- 1University of Illinois Chicago, Chicago, United States
- 2Norges teknisk-naturvitenskapelige universitet, Trondheim, Norway
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Inflammatory bowel disease (IBD) ulcerative colitis (UC) is characterized by continuous inflammation of the colon with erosion and ulcers. Diagnosis typically occurs in patients between their late teens and mid-30s with no cure. Available therapeutics are efficient at controlling symptoms however, they have many serious adverse effects. Thus, additional therapies with limited adverse effects are needed to complement these drugs. In this study, we evaluated the anti-inflammatory potential of carnosic acid (CA), the most abundant diterpene in rosemary (Salvia rosmarinus) and sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables. We used colonic epithelial organoids (colonoids) derived from non-IBD and UC patients as a physiologically relevant testing platform for both phytochemicals. These patient-derived colonoids are a representative model that recapitulates the parent epithelial tissue including its cellular composition and 3D structure. Moreover, we cultured the colonoids at 2% O2 to better approximate the low oxygen level (physioxia) observed in the colon crypts. To assess the effects of CA and SFN in the nuclear factor erythroid 2-related factor 2 (NRF2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, we studied modulation of inflammatory cytokines through a 40-plex chemokine assay and ELISA, as well as gene and protein expression of target genes with qPCR and western blot, respectively. Through these techniques, we observed that CA and SFN decreased inflammatory markers and promoted NRF2 activity in patient-derived colonoids. Additionally, SFN and CA modulated the expression and secretion of the NF-κB promoted antibacterial peptide neutrophil gelatinase-associated lipocalin which is highly expressed in the inflamed colonic epithelium and has been suggested as a biomarker for active UC.
Keywords: intestinal epithelial organoid, anti-inflammatory, inflammatory bowel disease, Nrf2, NGAL, LCN2
Received: 01 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Rivera Rodríguez, Sæterstad, Chattergoon Ali, Selvik, Bakke, Bruland and Johnson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jeremy James Johnson, jjjohn@uic.edu
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