Phyllanthin Targets GBP5 to Suppress Macrophage M1 Polarization and Alleviate DSS-Induced Colitis in a Murine Model

Collectively, our gain-of-function and loss-of-function experiments have confirmed that PHY is a promising therapeutic agent. It alleviates experimental colitis by targeting GBP5 to regulate M1 macrophage polarization and restore intestinal barrier function. Mechanistically, PHY may inhibit the enzymatic activity of GBP5 by engaging its GTP-binding pocket. This study not only identifies PHY as an attractive lead compound for the treatment of IBD but also provides robust experimental evidence that GBP5 is a promising therapeutic target for inflammatory diseases.