Ailanthone ameliorates CCl4-induced liver fibrosis by targeting PKM2-mediated macrophage M1 polarization and glycolytic reprogramming - PubMed
5 hours ago
- #Liver Fibrosis
- #PKM2 Targeting
- #Macrophage Polarization
- Ailanthone (AIL) reduces CCl4-induced liver fibrosis in mice by lowering collagen deposition and serum liver enzyme levels.
- AIL suppresses M1 macrophage polarization and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, iNOS) in LPS-stimulated RAW264.7 cells.
- AIL targets PKM2, inhibiting its expression and activity, and reduces aerobic glycolysis markers (lactate, GLUT-1, HIF-1α, LDHA).
- PKM2 knockdown or stabilization with TEPP-46 mimics AIL's effects, confirming PKM2 as a key anti-fibrotic target.
- AIL also inhibits TGF-β1-induced activation of hepatic stellate cells (LX-2), reducing extracellular matrix protein expression.
- The findings position AIL as a promising PKM2-directed therapy for liver fibrosis by modulating macrophage metabolism and polarization.