Neuroprotective effects of dehydroglyasperin C through increased expression of heme oxygenase-1 in mouse hippocampal cells

Abstract

. The objective of this study was to explore the neuroprotective effect of dehydroglyasperin C (DGC) againstglutamate-induced oxidative stress in the mouse hippocampal HT22 cells. DGC signiÞcantly reduced cytotoxicity and reactive oxygenspecies (ROS) generation induced by glutamate in HT22 cells, whereas DGC did not restore glutathione depletion caused by glutamate. Inaddition, we investigated further whether DGC affected the expression of heme oxygenase (HO)-1, one of major cellular antioxidantdefense systems, and found that DGC dose-dependently increased HO-1 expression. DGC-mediated cytoprotection of HT22 neuronal cellsfrom glutamate insult was abrogated by either HO-1 inhibitor (Tin protoporphyrin, SnPP) or AKT inhibitor (LY294002). In conclusion,the present results demonstrate for the Þrst time that DGC protects neuronal cells against glutamate-induced oxidative injury through theinduction of HO-1 expression which is, in turn, activated maybe through Nrf2-Keap1 and PI3K/AKT signaling pathways.