Angelicin: A promising tricyclic aromatic agent for ulcerative colitis through cysteine-mediated proliferation of intestinal epithelial cells

Angelicin (Ang), a natural tricyclic aromatic compound and quality marker derived from Fructus Psoraleae , exhibits significant anti-inflammatory efficacy. Fructus Psoraleae has long been utilized clinically for treating ulcerative colitis (UC). However, the specific role of Ang in UC remains poorly characterized. The present study aimed to elucidate the anti-UC effects of Ang and its underlying mechanisms. The anti-UC activity of Ang was evaluated using two UC models induced by dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS). Results demonstrated that Ang markedly inhibited the progression of UC. Microbial profiling indicated that the Ang-treated microbiome, particularly Lactobacillus murinus , provided protective effects against UC. Mechanistically, Ang facilitated proliferation of normal colonic epithelial cells, thus enhancing the intestinal mucosal barrier (IMB). Cysteine (Cys) played a crucial intermediary role by promoting glutathione (GSH) synthesis, maintaining redox homeostasis, and consequently facilitating cell proliferation. Additionally, increased Cys levels supported ribosomal biogenesis, enhancing protein translation and further stimulating cell proliferation. G-rich RNA sequence-binding factor 1 (GRSF1) was identified as a direct molecular target of Ang during ribosomal biogenesis. These findings indicated that Ang is a promising agent for promoting Cys-mediated cell proliferation, highlighting its role in maintaining redox homeostasis and protein translation. This study provides evidence supporting the future development of Ang as a therapeutic candidate for UC. • Angelicin significantly reduces the inflammation and repairs the damaged intestinal mucosal barrier in ulcerative colitis mice; • Angelicin restores gut microbiome in ulcerative colitis mice; • Angelicin promotes cell proliferation by resisting oxidative stress and promoting protein translation; • Angelicin is a promising target for future clinical research and a potential adjunct to traditional treatments.