Phyllanthin Targets GBP5 to Suppress Macrophage M1 Polarization and Alleviate DSS-Induced Colitis in a Murine Model - PubMed
2 days ago
- #Inflammatory Bowel Disease
- #Phyllanthin
- #Macrophage Polarization
- Phyllanthin (PHY), a bioactive lignan from Phyllanthus species, shows anti-inflammatory properties and potential for treating inflammatory bowel disease (IBD).
- PHY significantly alleviated DSS-induced colitis in mice, improving disease severity markers like body weight, DAI scores, and colon length in a dose-dependent manner.
- PHY restored intestinal barrier integrity by reducing permeability, repairing tight junctions, and upregulating proteins like ZO-1, Claudin-1, and MUC2.
- PHY selectively inhibited pro-inflammatory M1 macrophage polarization in both colonic tissues and in vitro, without promoting M2 macrophage markers.
- Mechanistically, PHY binds to the GBP5 GTPase domain, inhibiting its activity and counteracting its upregulation by LPS/IFN-γ, which is crucial for M1 polarization.
- GBP5 knockdown mimicked PHY's inhibitory effect on M1 polarization, while GBP5 overexpression worsened colitis, confirming GBP5 as a therapeutic target.
- PHY is identified as a promising lead compound for IBD treatment, with GBP5 highlighted as a potential therapeutic target for inflammatory diseases.