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

Life Sci. 2015 Jan 15:121:145-51. doi: 10.1016/j.lfs.2014.12.002. Epub 2014 Dec 11.

Abstract

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.

Keywords: Ginsenoside-Rg1; Middle cerebral artery occlusion; Neuroprotection; Protease-activated receptor-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Blood-Brain Barrier / drug effects
  • Cerebral Infarction / pathology
  • Cerebral Infarction / prevention & control
  • Down-Regulation / drug effects
  • Ginsenosides / pharmacology*
  • Male
  • Neuroprotective Agents / pharmacology*
  • Platelet Aggregation Inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, PAR-1 / biosynthesis
  • Reperfusion Injury / prevention & control*

Substances

  • Ginsenosides
  • Neuroprotective Agents
  • Receptor, PAR-1
  • ginsenoside Rg1
  • Platelet Aggregation Inhibitors