DGC protects neuronal cells against glutamate‐induced oxidative injury through the induction of HO‐1 expression

Abstract

Oxidative stress has been related to the development of chronic neurodegenerative diseases and acute neurological injury. Licorice, the root of the Glycyrrhiza species (Glycyrrhiza uralensis Fisher), is known to have antioxidant, anti‐inflammatory, anti‐viral, and anti‐tumor properties. The object of this study is to explore the neuroprotective effects of dehydroglyasperin C (DGC) against glutamate‐induced oxidative stress in the mouse hippocampal HT22 cells. DGC significantly reduced cytotoxicity and reactive oxygen species (ROS) generation induced by glutamate in HT22 cells, whereas DGC did not restore glutathione depletion caused by glutamate. In addition, we investigated further whether DGC affected the expression of heme oxygenase (HO)‐1, one of major cellular antioxidant defense system, and found that DGC dose‐dependently increased HO‐1 expression. DGC‐mediated cytoprotection of HT22 neuronal cells from glutamate insult was abrogated by either Tin protophorphyrin (SnPP), an inhibitor of HO‐1, or AKT inhibitor (LY294002). In conclusion, the present results demonstrate for the first time that DGC protects neuronal cells against glutamate‐induced oxidative injury through the induction of HO‐1 expression which is, in turn, activated by PI3k/AKT signaling pathway.