Morroniside protects HT-22 cells against oxygen-glucose deprivation/reperfusion through activating the Nrf2/HO-1 signaling pathway.

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a devastating condition that affects neurodevelopment and results in brain injury in infants. Morroniside (MOR), a natural secoiridoid glycoside, has been found to possess neuroprotective effect. However, the effects of MOR on neonatal HIE are unclear. An in vitro HIE model was established in murine hippocampal neurons HT-22 cells using oxygen-glucose deprivation/reoxygenation (OGD/R) stimulation. Our results showed that MOR improved OGD/R-caused cell viability reduction in HT-22 cells. MOR suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in OGD/R-induced HT-22 cells in a dose-dependent manner. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GP_X) were significantly elevated by MOR. Moreover, MOR treatment caused a significant increase in bcl-2 expression, and obvious decreases in the expression levels of bax, cleaved caspase-3, and cleaved caspase-9 expression. Furthermore, MOR significantly upregulated the expression levels of nuclear Nrf2 and HO-1 in OGD/R-treated HT-22 cells. Additionally, knockdown of Nrf2 or HO-1 abrogated the effects of MOR on OGD/R-induced oxidative stress and apoptosis in HT-22 cells. In conclusion, these findings suggested that MOR protects HT-22 cells against OGD/R via regulating the Nrf2/HO-1 signaling pathway.