Lycium barbarum glycopeptide attenuates ischaemic stroke by inhibiting inflammation via SIRT3-mediated NLRP3 deacetylation

Background Inflammatory processes play a critical role in ischaemic stroke. Acetylation of NLRP3 is a key step in amplifying neuroinflammation. (LbGP), a bioactive glycoprotein derived from Lycium barbarum, has anti-inflammatory potential, but its mechanisms in post-stroke neuroinflammation remain unclear. Aim: This study aimed to investigate the efficacy and molecular mechanisms of LbGP in alleviating neuroinflammation following ischaemic stroke. Methods A mouse model of middle cerebral artery occlusion (MCAO)/reperfusion was used to induce focal cerebral ischaemia/reperfusion (I/R) injury. Microglial cells were subjected to oxygen-glucose deprivation/reoxygenation. Neurological recovery was assessed by Y-maze and open-field tests. Molecular mechanisms were explored using Western blotting, ELISA, co-immunoprecipitation and immunofluorescence. Results LbGP significantly reduced cerebral infarct volume, attenuated neuroinflammation and improved functional recovery in I/R mice. Mechanistically, LbGP suppressed NLRP3 inflammasome activation through Sirtuin 3-mediated inhibition of NLRP3 acetylation, a finding further validated by exacerbated neuroinflammation in Sirt3-knockout mice. Conclusion This study demonstrates for the first time that LbGP alleviates post-stroke neuroinflammation via Sirt3-mediated deacetylation of NLRP3, thereby disrupting inflammasome activation, and identifies LbGP as a promising therapeutic candidate for ischaemic stroke.