Abstract
Microbiota-derived catabolism of nutrients is closely related to ulcerative colitis (UC). The level of indole-3-acetic acid (IAA), a microbiota-dependent metabolite of tryptophan, was decreased significantly in the feces of UC patients. Thus supplementation with IAA could be a potential therapeutic method for ameliorating colitis. In this work, the protective effect of supplementation with IAA on dextran sulfate sodium (DSS)-induced colitis was evaluated, and the underlying mechanism was elucidated. The results indicated that the administration of IAA significantly relieved DSS-induced weight loss, reduced the disease activity index (DAI), restored colon length, alleviated intestinal injury, and improved the intestinal tight junction barrier. Furthermore, IAA inhibited intestinal inflammation by reducing the expression of proinflammatory cytokines and promoting the production of IL-10 and TGF-β1. In addition, the ERK signaling pathway is an important mediator of various physiological processes including inflammatory responses and is closely associated with the expression of IL-10. Notably, IAA treatment induced the activation of extracellular signal-regulated kinase (ERK), which is involved in the progression of colitis, while the ERK inhibitor U0126 attenuated the beneficial effects of IAA. In summary, IAA could attenuate the clinical symptoms of colitis, and the ERK signaling pathway was involved in the underlying mechanism. Supplementation with IAA could be a potential option for preventing or ameliorating UC.
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Acknowledgements
This research was supported by the National Natural Science Foundation of China (Grant No. 82100555 and 82071861), the Natural Science Foundation of Shandong Province (Grant No. ZR2022QH051), the University and Institute Innovation Team Project of Jinan (Grant No. 2020GXRC036), the Innovation Pilot Project of Integration of Science, Education and Industry (Grant No. 2022PY068 and 2022JBZ02-04), and the Talent Project from Qilu University of Technology (Grant No. 2023RCKY085).
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Qu, X., Song, Y., Li, Q. et al. Indole-3-acetic acid ameliorates dextran sulfate sodium-induced colitis via the ERK signaling pathway. Arch. Pharm. Res. 47, 288–299 (2024). https://doi.org/10.1007/s12272-024-01488-z
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DOI: https://doi.org/10.1007/s12272-024-01488-z