Polygalasaponin F inhibits neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation through the PI3K/Akt pathway

Basic Clin Pharmacol Toxicol. 2020 Sep;127(3):196-204. doi: 10.1111/bcpt.13408. Epub 2020 Apr 13.

Abstract

Cerebral ischaemia is a common cerebrovascular disease and often induces neuronal apoptosis, leading to brain damage. Polygalasaponin F (PGSF) is one of the components in Polygala japonica Houtt, and it is a triterpenoid saponin monomer. This research focused on anti-apoptotic effect of PGSF during oxygen-glucose deprivation and reoxygenation (OGD/R) injury in rat adrenal pheochromocytoma cells (PC12) and primary rat cortical neurons. OGD/R treatment reduced viability of PC12 cells and primary neurons. This reduced viability was prevented by PGSF, as shown by MTT assay. OGD/R insult decreased expression of Bcl-2/Bax both in PC12 cells and primary neurons but elevated levels of caspase-3 in primary neurons. However, PGSF may up-regulate expression of Bcl-2/Bax and down-regulate caspase-3 in these particular cells. Furthermore, Bcl-2/Bax and the ratio between phosphorylated Akt and total Akt were decreased in PC12 cells treated with OGD/R, and both were increased by PGSF. Moreover, increase in the ratios of Bcl-2/Bax and phosphorylated Akt/total Akt in PC12 cells was suppressed by phosphatidylinositol 3-kinase (PI3K) inhibitor. Data suggest PGSF might prevent OGD/R-induced injury via activation of PI3K/Akt signalling. The ability of PGSF to block the effects of OGD/R appears to involve regulation of Bcl-2, Bax and caspase-3, which are related to apoptosis.

Keywords: anti-apoptosis; neurons; oxygen-glucose deprivation and reoxygenation (OGD/R); phosphatidylinositol 3-kinase (PI3K)/Akt; polygalasaponin F (PGSF).

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Survival / drug effects
  • Glucose / metabolism
  • Male
  • Neurons / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Oncogene Protein v-akt
  • Oxygen / metabolism
  • PC12 Cells
  • Phosphatidylinositol 3-Kinase / metabolism
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Signal Transduction / drug effects
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Apoptosis Regulatory Proteins
  • Neuroprotective Agents
  • Saponins
  • Triterpenes
  • polygalasaponin F
  • Phosphatidylinositol 3-Kinase
  • Oncogene Protein v-akt
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • Oxygen