Ligustilide ameliorates neuroinflammation and brain injury in focal cerebral ischemia/reperfusion rats: involvement of inhibition of TLR4/peroxiredoxin 6 signaling

摘要: Blocking TLR4/peroxiredoxin (Prx6) signaling is proposed to be a novel therapeutic strategy for ischemic stroke because extracellular Prx6 released from cells may act as an endogenous ligand TLR4 and initiate destructive immune responses in brain. Our previous studies showed that ligustilide (LIG) exerted antineuroinflammatory neuroprotective effects against insult, but the underlying mechanisms remain unclear. This study investigated whether TLR4/Prx6 pathway involved protective effect of LIG postischemic neuroinflammation brain injury induced by transient middle cerebral artery occlusion (MCAO) rats. Intraperitoneal administration (20 40 mg/kg/day) at reperfusion onset after MCAO resulted reduction infarct size improved neurological outcome over 72 h. LIG-induced neuroprotection was accompanied improvement neuropathological alterations, including neuron loss, astrocyte microglia/macrophage activation, neutrophil T-lymphocyte invasion, regulation inflammatory mediators expression. Moreover, significantly inhibited expression release activation signaling, reflected decreased expression, signal-regulated kinase 1/2 phosphorylation, transcriptional activity NF-κB signal transducer activator transcription 3 results demonstrate provide early direct inhibiting subsequent immunity ischemia. These findings support translational potential blocking treatment stroke.