Identification of potential mechanisms of ferulic acid in inflammatory bowel disease through integrated network pharmacology and experimental validation.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the digestive tract, and ferulic acid (FA), a phenolic compound with anti-inflammatory activity, has emerged as a promising therapeutic candidate. In this study, we combined bioinformatics analyses with in vitro molecular experiments to elucidate the anti-inflammatory effects and potential mechanisms of FA in IBD. An IBD-like cellular model was established by stimulating human intestinal epithelial NCM460 cells with lipopolysaccharide (LPS), and the effects of FA on inflammatory cytokines were assessed using ELISA, RT-qPCR, and Western blot. Bioinformatics screening identified STAT3 as a potential target associated with FA-mediated anti-inflammatory activity in IBD. We found that FA markedly downregulated inflammatory cytokines, including IL-6 and TNF-α, and further experimental evidence indicated that FA significantly inhibited the phosphorylation of STAT3, JAK1, and JAK2. Docking simulations showed that FA could embed in the STAT3 binding pocket with a moderate docking score. Collectively, these findings support FA as a low-toxicity candidate modulator of JAK/STAT signaling with potential therapeutic relevance to IBD.