Abstract: Our previous studies reported the anti-neuroinflamatory and neuroprotective effects of Z-ligustilide(LIG).The interaction between peroxisome proliferatoractivated receptor γ(PPARγ) and TLR4/NF-κB signaling is associated with neuroinflammatory response and inflammatory injury in brain.The present study is to investigate whether PPARγ-modulating TLR4/NF-κB signaling pathway is implicated in the molecular mechanism of LIG anti-neuroinflammation.Male rats were pretreated with vehicle,LIG,or GW9662(selective PPARγ antagonist) plus LIG,followed by the intracerebroventricular injection of lipopolysaccharide(LPS,a TLR4 ligand).The results showed that LIG dose-dependently reduced LPS-induced increase in the concentrations of pro-inflammatory mediators(tumor necrosis factor α,monocyte chemoattractant protein-1),TLR4 protein expression in rat cerebral cortex.Moreover,LIG significantly prevented LPS-induced alterations in the transcription activities of NF-κB and PPARγ in the rat cortex.Remarkably,the anti-neuroinflammatory effects of LIG were effectively attenuated by GW9662,as indicated by an obvious increase in production of pro-inflammatory mediators and activation of TLR4/NF-κB signaling pathway following co-treatment with LIG and GW9662.Taken together,these findings suggested that LIG may prevent neuroinflammatory response through TLR4/NF-κB signaling inhibition in a PPARγ-dependent manner.

Key words: LIG, LPS, neuroimflammation, TLR4/NF-&kappa, B, PPAR&gamma