Pachymic acid protects against cerebral ischemia/reperfusion injury by the PI3K/Akt signaling pathway

Metab Brain Dis. 2020 Apr;35(4):673-680. doi: 10.1007/s11011-020-00540-3. Epub 2020 Mar 5.

Abstract

Pachymic acid (PA) from medicinal fungus Poria cocos has a variety of pharmacological potentials. However, there are no reports of the effects of PA on cerebral ischemia/reperfusion (I/R) injury. The purpose of this study was to investigate the mechanisms of PA on cerebral I/R injury in rats. The effects of PA on cerebral infarction size, brain water content, neurological symptoms and cerebral blood flow were evaluated. Nissl staining was used to observe the damage of ischemic brain neurons after I/R in rats. Apoptosis of ischemic brain neurons after I/R was observed by TUNEL staining. The effect of PA on the expression of some components of PI3K/Akt was detected by Western blotting. PA significantly increased cerebral blood flow after I/R in rats, reduced infarct volume and brain water content, and downgrade neurological function scores, significantly reduced neuronal damage after I/R in rats, and significantly decreased neuronal apoptosis. The effect of PA on rat I/R can be eliminated by LY294002. In addition, PA significantly up-regulated the protein expression of p-PTEN (Ser380), p-PDK1 (Ser241), p-Akt (Ser473), pc-Raf (Ser259) and p-BAD (Ser136), and down-regulated Cleaved caspase protein expression. LY294002 can reverse the effect of PA on the expression of PI3K / Akt signaling pathway related protein in rats after I/R. PA had obviously neuroprotective effects on brain I/R injury and neuronal apoptosis, and its mechanism may be related to activation of PI3K / Akt signaling pathway.

Keywords: Apoptosis; Citric acid; I/R injury; PI3K / Akt.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Ischemia / metabolism*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use

Substances

  • Neuroprotective Agents
  • Triterpenes
  • Proto-Oncogene Proteins c-akt
  • pachymic acid