Coixol inhibits the IL17A signaling pathway and promotes mitophagy to improve ulcerative colitis

Coicis Semen , a versatile food known for its nutraceutical properties, is valued for its edibility. Coixol, the principal bioactive component of Coicis Semen , exhibits potent anti-inflammatory effects, highlighting its potential in managing inflammatory diseases. This study investigates the efficacy of Coixol in alleviating ulcerative colitis (UC) and describes its underlying mechanisms. By integrating network pharmacology with transcriptome profiling, we demonstrate that Coixol modulates genes involved in interleukin (IL)17 A signaling pathway and autophagy. We also predict the binding potential of Coixol and its target proteins using molecular docking. We found that Coixol notably reduced weight loss, colonic injury, inflammatory cytokines, and mitochondrial damage in dextran sulfate sodium (DSS)-induced mice. Moreover, Coixol greatly inhibited the IL17A signaling pathway and boosted mitophagy-related gene and protein expressions in both DSS-induced mice and IL17A-stimulated RAW264.7 cells. Molecular docking further revealed Coixol's ability to bind tightly and stably to IL17A, IL17RA, TNF receptor-associated factor 6 (TRAF6), nuclear factor kappa-B (NF-κB), and Inhibitor of Nuclear Factor κB alpha‌ (IKBα). Taken together, these data suggest that Coixol's therapeutic potential in UC is mediated by its inhibition of the IL17A signaling pathway and interactions with relevant targets, thus promoting mitophagy. This positions Coixol as a functional food candidate for managing UC. • Coixol as a natural nutrient could effectively improve ulcerative colitis. • Coixol could activate mitophagy by inhibiting IL17A signaling pathways . • Provide an effective therapeutic strategy for alleviating UC.