Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression

Phytomedicine. 2014 Jun 15;21(7):998-1003. doi: 10.1016/j.phymed.2013.12.005. Epub 2014 Jan 22.


Ginsenoside Rg1 is regarded as one of main bioactive compounds responsible for pharmaceutical actions of ginseng with little toxicity and has been shown to have possibly neuroprotective effects. However, the mechanism of its neuroprotection for acute ischemic stroke is still elusive. The purpose of present study is thus to assess the neuroprotective effects of the ginsenoside Rg1 against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion, and then to explore the mechanisms for these neuroprotective effects by targeting aquaporin 4. Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longa's 5-point scale. Evans blue dye was used to investigate the effects of ginsenoside Rg1 on blood brain barrier permeability. Immunohistochemical analysis and real-time fluorescence quantitative polymerase chain reaction were used to assess aquaporin 4 expression. As a result, general linear model with repeated measures analysis of variance for neurological scores at 5 repeated measures showed that ginsenoside Rg1-treated group could significantly reduce the changing trend of neurological deficit scores when compared with the middle cerebral artery occlusion model group (p<0.05). Compared with the middle cerebral artery occlusion model group, ginsenoside Rg1 group has significantly decreased Evans blue content and reduced aquaporin 4 expression at each time point (p<0.05). In conclusion, ginsenoside Rg1 as a ginsenoside neuroprotective agent could improve neurological injury, attenuate blood brain barrier disruption and downregulate aquaporin 4 expression induced by cerebral ischemia/reperfusion insults in rats.

Keywords: Aquaporin 4; Blood brain barrier disruption; Ginsenoside Rg1; Neuroprotection; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / genetics
  • Aquaporin 4 / metabolism
  • Blood-Brain Barrier / drug effects*
  • Brain Ischemia / drug therapy*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects
  • Ginsenosides / pharmacology*
  • Male
  • Neuroprotective Agents / pharmacology*
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / prevention & control*


  • Aqp4 protein, rat
  • Aquaporin 4
  • Ginsenosides
  • Neuroprotective Agents
  • ginsenoside Rg1