Therapeutic potential of tryptophan metabolite indoleacrylic acid in inflammatory bowel disease: From cellular mechanisms to zebrafish stress-like behavior.

Inflammatory bowel disease (IBD) is a chronic condition associated with elevated rates of anxiety and depression and ultimately reduces the quality of life. Thus, preventive care addressing both physical and psychological health is essential. In this study we aimed to explore the protective effects of Indoleacrylic Acid (IA) against lipopolysaccharide (LPS)-induced inflammation using human colorectal adenocarcinoma cells (HT-29) and dextran sulfate sodium (DSS)-induced zebrafish to assess its potential as a novel therapeutic agent for IBD. IA exhibited substantial anti-inflammatory properties in HT-29 cells and zebrafish models. It significantly reduced the production of pro-inflammatory mediators, including PGE, TNF-α, IL-6, and IL-8, while upregulating MUC2, AhR, and tight junction proteins (ZO-1, occludin, and claudin-1), thereby enhancing mucosal barrier integrity. In zebrafish larvae, IA improved survival rates, boosted mucin production, and reduced macrophage infiltration and heartbeat rate. Behavioral analyses of adult zebrafish revealed that IA alleviated anxiety-like behaviors, as shown by increased locomotion and improved performance in zone preference and light-dark transition tests. By targeting inflammation and anxiety-like symptoms, IA demonstrates a dual benefit by addressing both intestinal inflammation and the psychological burden of IBD. These findings highlight IA's potential as a novel therapeutic agent for managing IBD, offering a comprehensive approach to improving patient outcomes.