Pseudopterosin A ameliorates ischaemia-induced brain injury by acting on Akt signalling pathway

Folia Neuropathol. 2018;56(2):104-111. doi: 10.5114/fn.2018.76614.

Abstract

Introduction: Brain injury caused by ischaemic stroke is a major cause of disability and death throughout the world. The present study evaluates the neuroprotective effect of pseudopterosin A (PtA) against ischaemia-induced brain injury.

Material and methods: Ischaemia was induced by pMCAO model, and rats were separated in to three groups. A control group; an ischemic group receiving saline solution; and a PtA group receiving PtA (5 mg/kg, i.p.) for the period of three days, i.e. two days before surgery and after the surgery. Effect of PtA was assessed by estimating the infract volume and neurological deficits. Level of oxidative stress, inflammatory mediators, and markers of apoptosis were estimated in the brain tissues. Western blot assay and immunohistochemistry was done for the assessment of expressions of protein.

Result: Data from the study suggest that treatment with PtA significantly decreases the infracted volume and neurological deficit score compared to the ischaemic group. Treatments with PtA attenuate the activity of antioxidant enzyme, and the level of inflammatory mediators and markers of apoptosis in the brain tissues of ischaemia-induced brain injury. Phosphorylation of FKHR, Bad, and Akt were significantly reduced in the PtA-treated group compared to the ischaemic group.

Conclusions: The present study shows that pseudopterosin A attenuates neuronal injury in the pMCAO model by acting on the Akt signalling pathway.

Keywords: Akt signalling; apoptosis; brain injury; pseudopterosin A.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / metabolism*
  • Diterpenes / pharmacology*
  • Glycosides / pharmacology*
  • Male
  • Neuroprotective Agents / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Signal Transduction / drug effects*

Substances

  • Diterpenes
  • Glycosides
  • Neuroprotective Agents
  • pseudopterosins
  • Proto-Oncogene Proteins c-akt