Magnoflorine, a dietary alkaloid from Alpinia oxyphylla fruit, ameliorates colitis by restoring intestinal barrier and dual modulation of JAK/STAT3 pathway.

Inflammatory bowel disease (IBD) management necessitates novel, diet-compatible therapeutics. Using untargeted metabolomics, we identified magnoflorine as the key anti-colitis alkaloid from the edible fruit Alpinia oxyphylla. Integrated network pharmacology, molecular docking, and a zebrafish colitis model revealed that magnoflorine directly binds to core targets including SRC and STAT3. In DSS-induced colitis, magnoflorine restored intestinal barrier integrity (upregulating ZO-1, occludin, and mucin) and rebalanced inflammatory responses (suppressing TNF-α and IL-6 while promoting IL-22 and defensin-1). Mechanistically, magnoflorine not only inhibited JAK/STAT3 phosphorylation but also upregulated endogenous negative regulators PTPN6 and PIAS3, revealing a dual-modulatory strategy. These findings establish magnoflorine as a promising diet-derived candidate for IBD, supporting its development as a functional food ingredient.