Lycium ruthenicum Murr polysaccharide protects cortical neurons against oxygen-glucose deprivation/reperfusion in neonatal hypoxic-ischemic encephalopathy

Int J Biol Macromol. 2020 May 4:158:562-568. doi: 10.1016/j.ijbiomac.2020.04.122. Online ahead of print.

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a complex condition that remains the leading cause of mortality and morbidity among infants. Polysaccharide has been reported to possess diverse biological activities, however, the neuro-protective activity of polysaccharide isolated from Lycium ruthenicum remains unknown so far. However, the role of Lycium ruthenicum polysaccharide 3 (LRP3) in HIE has not been evaluated. Herein, we investigated the effect of LRP3 on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced primary cortical neurons. Our results demonstrated that LRP3 significantly improved the cell viability of OGD/R-induced cortical neurons. The OGD/R-caused increase in ROS production and decrease in the activities of anti-oxidative enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were mitigated by LRP3. Besides, the caspase-3 activity in OGD/R-induced cortical neurons was markedly decreased after LRP3 treatment. The increased bax expression and decreased bcl-2 expression caused by OGD/R stimulation were alleviated by pretreatment with LRP3. In addition, LRP3 significantly induced the expressions of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in OGD/R-induced cortical neurons. However, inhibition of Nrf2/HO-1 signaling pathway through transfection with siRNA targeting Nrf2 reversed the protective effects of LRP3. In conclusion, LRP3 exerts a neuroprotective effect against OGD/R-induced neuronal injury in rat primary cortical neurons.

Keywords: Hypoxic-ischemic injury; L. ruthenicum polysaccharide 3 (LRP3); Neonatal hypoxic-ischemic encephalopathy (HIE); Nrf2/HO-1 signaling pathway; Oxidative stress.