Chronopharmacological effects of 5-aminosalicylic acid in the treatment of experimental colitis in mice
- 1Chinese Medicine Guangdong Laboratory (Hengqin), State Key Laboratory of Traditional Chinese Medicine Syndrome, Key Laboratory of Chinese Medicinal Resource from Lingnan, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine , ,
Abstract
Background: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis, but whether dosing timing influences its therapeutic efficacy remains unclear. This study aims to investigate the chronopharmacological effects of 5-ASA in experimental colitis.
Methods: A dextran sulfate sodium (DSS)-induced colitis model was used to compare the therapeutic effects of 5-ASA administered at different Zeitgeber times. Colonic proteomic profiling was performed to identify circadian-responsive proteins associated with differential drug efficacy. Intestinal epithelial-specific Bmal1 knockout mice were used to determine whether the circadian clock regulates the chronopharmacological response to 5-ASA.
Results: 5-ASA showed marked time-dependent efficacy in DSS-induced colitis, with greater protection at ZT14 than at ZT2. Proteomic analysis identified ferritin heavy chain 1 (FTH1) as a circadian-responsive protein associated with differential treatment outcomes. 5-ASA suppressed FTH1 expression, whereas FTH1 overexpression attenuated anti-inflammatory effects of 5-ASA. Moreover, intestinal epithelial-specific deletion of Bmal1 largely abolished diurnal variation in both FTH1 expression and 5-ASA efficacy, indicating that the intestinal clock coordinates the time-dependent response to 5-ASA.
Conclusion: These findings identify FTH1 as a circadian-responsive factor linked to the time-dependent efficacy of 5-ASA and support circadian-guided optimization of 5-ASA administration as a potential strategy for improving UC treatment.
Related
- 5-Aminosalicylic Acid-induced Colitis in a Patient with Rheumatoid Arthritis without Inflammatory Bowel Disease
- Gene and microRNA Expression Profiling in Experimental Colitis and Human Ulcerative Colitis: Effects of STAT6 Knockout and Corylus avellana Treatment
- Hydatid Cyst Fluid of Echinococcus granulosus Alleviates Experimental Ulcerative Colitis by Suppressing Inflammation and Oxidative Stress and Regulating the Gut Microbiota
- ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment
- Integrative network pharmacology, machine learning, and experimental validation reveal the protective potential and potential molecular mechanisms of orientin in DSS-induced colitis
BibTeX
@article{wen2026chronopharmacological,
title = {{Chronopharmacological effects of 5-aminosalicylic acid in the treatment of experimental colitis in mice}},
author = {Yulin Wen and Shuangye Li and Jincan Jian and Jiahui Liu and Shuai Wang and Haomeng Wu},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1936952},
url = {https://europepmc.org/article/PMC/PMC13671935},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chronopharmacological effects of 5-aminosalicylic acid in the treatment of experimental colitis in mice
AU - Yulin Wen
AU - Shuangye Li
AU - Jincan Jian
AU - Jiahui Liu
AU - Shuai Wang
AU - Haomeng Wu
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1936952
UR - https://europepmc.org/article/PMC/PMC13671935
AB - Background: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis, but whether dosing timing influences its therapeutic efficacy remains unclear. This study aims to investigate the chronopharmacological effects of 5-ASA in experimental colitis. Methods: A dextran sulfate sodium (DSS)-induced colitis model was used to compare the therapeutic effects of 5-ASA administered at different Zeitgeber times. Colonic proteomic profiling was performed to identify circadian-responsive proteins associated with differential drug efficacy. Intestinal epithelial-specific Bmal1 knockout mice were used to determine whether the circadian clock regulates the chronopharmacological response to 5-ASA. Results: 5-ASA showed marked time-dependent efficacy in DSS-induced colitis, with greater protection at ZT14 than at ZT2. Proteomic analysis identified ferritin heavy chain 1 (FTH1) as a circadian-responsive protein associated with differential treatment outcomes. 5-ASA suppressed FTH1 expression, whereas FTH1 overexpression attenuated anti-inflammatory effects of 5-ASA. Moreover, intestinal epithelial-specific deletion of Bmal1 largely abolished diurnal variation in both FTH1 expression and 5-ASA efficacy, indicating that the intestinal clock coordinates the time-dependent response to 5-ASA. Conclusion: These findings identify FTH1 as a circadian-responsive factor linked to the time-dependent efficacy of 5-ASA and support circadian-guided optimization of 5-ASA administration as a potential strategy for improving UC treatment.
SN - 1664-3224
ER -