Panax notoginsenoside saponins Rb1 regulates the expressions of Akt/ mTOR/PTEN signals in the hippocampus after focal cerebral ischemia in rats

Behav Brain Res. 2018 Jun 1:345:83-92. doi: 10.1016/j.bbr.2018.02.037. Epub 2018 Mar 6.

Abstract

Panax notoginsenoside saponins Rb1 (PNS-Rb1) is an important active ingredient of panax notoginseng for effective treatment of cerebrovascular diseases. However, the mechanism underlying its actions in the state of cerebral ischemia is still unclear. We asked whether the potential neuroprotection of PNS-Rb1 on the brain is due to, at least partially, its modulation of AkT/mTOR/PTEN signalling pathway along with down-regulation of caspase-3 in rats subjected to phototrombic stroke. To test this hypothesis, rats with induced photothrombotic stroke were treated with PNS-Rb1 (applied in three different doses, 25 mg/kg, 50 mg/kg,100 mg/kg, respectively) or saline, while sham operated rats injected with saline were used as the control. Our results indicate that PNS-Rb1 significantly alleviated the morphological lesion concomitant with improvement of cognitive and sensorimotor deficits induced by ischemic stroke. Moreover, immunohistochemistry and Western blot analyses showed that PNS Rb1 in a dose dependent manner increased the expressions of P-Akt, P-mTOR and reduced P-PTEN and caspase-3. The present study suggests that the improvement of cognitive and sensorimotor deficits by PNS-Rb1 is made, at least partially, by the modulation of the Akt/mTOR/PTEN signalling pathway.

Keywords: Akt/mTOR/PTEN; Focal cerebral ischemia; Hippocampus; Panax notoginsenoside Rb1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / psychology
  • Caspase 3 / metabolism
  • Cognition / drug effects
  • Cognition / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • PTEN Phosphohydrolase / metabolism
  • Panax notoginseng
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Saponins / pharmacology
  • Saponins / therapeutic use*
  • Signal Transduction / drug effects
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / psychology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Neuroprotective Agents
  • RNA, Messenger
  • Saponins
  • saponin Rb1, Panax notoginsenoside
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • Pten protein, rat
  • Casp3 protein, rat
  • Caspase 3