Paeoniflorin ameliorates oxidase stress in Glutamate-stimulated SY5Y and prenatally stressed female offspring through Nrf2/HO-1 signaling pathway

J Affect Disord. 2021 Nov 1:294:189-199. doi: 10.1016/j.jad.2021.07.054. Epub 2021 Jul 17.

Abstract

Background: Prenatal stress (PS) can cause brain retardation, reduce the learning and memory ability of the offspring and significantly increase the incidence of depression in offspring. Paeoniflorin (PF), a kind of monoterpenoid glycoside, is one of the main active ingredients of Chinese Medicine Paeonia lactiflora Pall, has anti-inflammation and potential neuroprotective effects. However, few reports have shown that the neuroprotective effects of PF are exerted through ameliorating Glutamate toxicity in vivo and in vitro.

Methods: Here, we used a prenatal restraint stress model and Glu-induced excitotoxic neurotoxicity in SH-SY5Y cells to study the effects of PF.

Results: Our results showed that PF can ameliorate learning and memory impairments and increases the density of hippocampal neurons, typical Golgi-positive pyramidal cells, and neuronal Neurogranin (Ng) expression in PS rat offspring. Furthermore, PF can significantly up-regulate the decrease of Glu-induced SH-SY5Y cell viability. At the same time, PF can significantly reduce apoptosis, ROS, NO levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. Besides, PF significantly increased the expression of Nrf2 and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active-caspase-3, and active-caspase-9.

Conclusions: Our results demonstrate that PF may be an effective treatment in preventing the development of PS-induced learning and memory impairment and have therapeutic potential in Glu-related neurological diseases.

Keywords: Glutamate; Nrf2; Paeoniflorin; SH-SY5Y; oxidase stress; prenatal stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Female
  • Glucosides
  • Glutamic Acid
  • Heme Oxygenase (Decyclizing)
  • Monoterpenes / pharmacology
  • NF-E2-Related Factor 2* / metabolism
  • NF-E2-Related Factor 2* / pharmacology
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress
  • Oxidoreductases
  • Pregnancy
  • Rats
  • Signal Transduction

Substances

  • Glucosides
  • Monoterpenes
  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Nfe2l2 protein, rat
  • peoniflorin
  • Glutamic Acid
  • Oxidoreductases
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat