Polydatin modulates inflammation by decreasing NF-κB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood-brain barrier permeability for its neuroprotective effect in pMCAO rat brain

Inflammation and oxidative stress play an important role in cerebral ischemic pathogenesis. Polydatin has been proved to elicit numerous biological effects through its anti-inflammatory and anti-oxidant properties. However, little is known regard to the mechanism of polydatin's neuroprotection in ischemic stroke. We therefore investigated the potential neuroprotective effects of polydatin and explored the underlying mechanisms. Male, Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO). Experiment 1 was used to evaluate the expression of glioma-associated oncogene homolog1 (Gli1), Patched-1 (Ptch1) and Superoxide dismutase 1 (SOD1) after pMCAO, six time points were included. Experiment 2 was used to detect polydatin's neuroprotection after pMCAO. Neurological deficit, brain water content and infarct size were measured at 24 h and 72 h after pMCAO. Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), Western Blotting, activity assay and confocal microscope were used to analyse the expression of Gli1, Ptch1, SOD1 and nuclear factor-kappa B (NF-kappa B). Experiment 3 was used to detect polydatin's influence on blood-brain barrier (BBB). Compared with Sham group, the expression of Gli1, Ptch1 and SOD1 were up-regulated shortly after pMCAO (P<0.05). Compared with Vehicle group, high dose of polydatin (50 mg/kg) up-regulated Gli1, Ptch1, SOD1 and down-regulated NF-kappa B, and reduced infarct volume, brain water content and behavioral deficits (P<0.05). Meanwhile, BBB permeability was also ameliorated. The results indicated that polydatin protected the brain from damage caused by pMCAO, and this effect may be through up-regulating the expression of Gli1, Ptch1 and SOD1 and down-regulating the expression of NF-kappa B, and ameliorating BBB permeability. (C) 2011 Elsevier Inc. All rights reserved.