Mechanistic Study of Jaceosidin in Regulating Secondary Inflammation After Spinal Cord Injury in Mouse by Inhibiting PKM2 Activity.

Abstract

Excessive pro-inflammatory polarization of microglia is a critical driver of secondary inflammation following spinal cord injury (SCI). Jaceosidin, a natural flavonoid with established anti-inflammatory properties, has not been extensively studied in the context of post-SCI inflammation regulation. Given the fundamental role of glycolysis in cellular energy metabolism and its crucial involvement in inflammatory processes, this study investigated the effects of Jaceosidin. We demonstrated that Jaceosidin significantly attenuated the inflammatory response in lipopolysaccharide-stimulated microglia in vitro. Subsequent in vitro and in vivo experiments revealed that Jaceosidin shifted microglial polarization away from the inflammatory state and suppressed glycolytic flux. Mechanistically, Jaceosidin directly targeted and inhibited the activity of pyruvate kinase M2 (PKM2), a key glycolytic enzyme. Intervention with Jaceosidin in a mouse SCI model resulted in reduced microglial activation at the injury site, diminished tissue damage, and significantly improved motor and autonomic nerve function recovery. In conclusion, our findings indicate that Jaceosidin mitigates microglial inflammation and promotes functional recovery after SCI by inhibiting PKM2 activity and dampening glycolysis. As a natural phytochemical derived from traditional Chinese medicine, Jaceosidin presents a promising novel therapeutic strategy for the clinical management of spinal cord injury.