Neuroprotective effect of ginsenoside-Rg1 on cerebral ischemia/reperfusion injury in rats by downregulating protease-activated receptor-1 expression

Aims: Ginsenoside-Rg1 (G-Rg1), a saponin that is a primary component of ginseng, is very useful and important in traditional Chinese medicine for stroke. The objective of this study was to explore the mechanisms underlying the neuroprotective effect of G-Rg1 on focal cerebral ischemia/reperfusion. Main methods: Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longa's 5-point scale. The brain infarct volume was determined by the 2,3,5-triphenyltetrazolium chloride staining. The permeability of the blood-brain barrier (BBB) was evaluated by Evans blue dye. Western blot and quantitative RT-PCR were used to assess protease-activated receptor-1 (PAR-1) expression. Key findings: After G-Rg1 treatment, there was a significant decrease in the neurobehavioral function score compared with normal saline (NS) treatment after ischemia/reperfusion (P <0.05). G-Rg1 significantly reduced the infarct volume compared with NS treatment after ischemia/reperfusion (P <0.001). The permeability of the BBB was significantly decreased in the G-Rg1 group compared with the NS group (P <0.05 or P <0.01). Western blot and quantitative real time RT-PCR indicated that G-Rg1 administration down-regulated the expression of PAR-1 in the ischemic hemisphere compared with NS administration (P <0.01 and P <0.05, respectively). The level of PAR-1 expression strongly correlated with BBB permeability in both the G-Rg1- and NS-treated rats (r = 0.856 and r = 0.908, respectively, P <0.01). Significance: G-Rg1 may ameliorate the neurological injury, the brain infarct volume and the BBB permeability induced by focal cerebral ischemia in rats and its neuroprotective mechanism is related to the down-regulation of PAR-1 expression. (c) 2014 Elsevier Inc. All rights reserved.