Forsythoside E Alleviates Liver Injury by Targeting PKM2 Tetramerization to Promote Macrophage M2 Polarization.

ABSTRACT: Sepsis-induced liver injury is closely associated with poor prognosis  in septic patients. In this study, through integrated approaches including high-throughput virtual screening, target fishing technology, and atomic force microscopy (AFM) analysis, Forsythiaside E (FE) is first identified as a novel allosteric activator of pyruvate kinase M2 (PKM2) that promotes tetramer formation. Mutant protein construction combined with dynamic light scattering (DLS) and fluorescence resonance energy transfer (FRET) reveals FE binds to PKM2 K311 to promote tetramer formation. Employing Seahorse XF metabolic analyzers, real-time single-cell multi-modal analysis systems, and transcriptome sequencing, it is revealed that FE-mediated PKM2 tetramerization induces metabolic reprogramming in macrophages whi

SUBMITTER: Wu B 

PROVIDER: S-EPMC12866822 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature