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

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 antiinflammation 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 activecaspase-9. Conclusions: Our results demonstrate that PF may be an effective treatment in preventing the development of PSinduced learning and memory impairment and have therapeutic potential in Glu-related neurological diseases.

Automated summary

The research showed that PF could improve learning and memory impairments in offspring of prenatal stress rats, increase hippocampal neuron density and typical Golgi-positive pyramidal cells, and neuronal Neurogranin (Ng) expression. Additionally, PF significantly up-regulated the decrease in Glu-induced SH-SY5Y cell viability.