The effect of Naringin on cognitive function, oxidative stress, cholinergic activity, CREB/BDNF signaling and hippocampal cell damage in offspring rats with utero-placental insufficiency-induced intrauterine growth restriction

Abstract

Intrauterine growth restriction (IUGR) induced by utero-placental insufficiency (UPI) results in delayed neural development and impaired brain growth. This study investigates the effects of Naringin (Nar) on memory, learning, cholinergic activity, oxidative stress markers, hippocampal CREB/BDNF signal pathway and cell damage in offspring of rats exposed to UPI. Twenty pregnant Wistar rats were randomly assigned to four groups: control, sham surgery, UPI + NS (UPI + normal saline as a vehicle), and UPI + Nar (UPI + Nar at 100 mg/kg/day). UPI was induced by permanently occluding the uterine anterior vessels on embryonic day (ED) 18. Naringin or saline was administered orally from ED15 to ED21. Behavioral assessments of offspring, including working memory, avoidance learning, and anxiety-like behavior, were conducted on a postnatal day (PND) 21. Subsequently, hippocampal acetylcholinesterase (AChE) activity, catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), hippocampal transcript level of cyclic AMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) and apoptotic neuron density in the hippocampus were evaluated. Naringin-treated rats demonstrated significant improvements in working and avoidance memory, increases in CAT, SOD, and TAC, CREB, BDNF and reductions in AChE activity, MDA levels, apoptotic neuron density, and anxiety-like behaviors compared to the UPI + NS group (p < 0.05). Naringin mitigates hippocampal cell damage, cognitive impairments, and anxiety by enhancing antioxidant defenses, modulating cholinergic activity and CREB/BDNF signaling in the brains of UPI-exposed offspring.