Protective effect of an ethanol extract mixture of Aralia elata, Chaenomeles sinensis fruit, and Glycyrrhizae radix against cerebral ischemia-reperfusion injury in rats and excitotoxic and oxidative neuronal damage

Abstract

Aralia elata, Chaenomeles sinensis fruit, and Glycyrrhizae radix have been widely used as oriental medicinal plants in Korea, China and Japan and found to possess anti-oxidative and anti-inflammatory activities. The current study was conducted to investigate the neuroprotective effect of an ethanol extract of a mixture of A. elata, C. sinensis fruit, and Glycyrrhizae radix (ACG) against ischemia-induced brain injury in rats and excitotoxic and oxidative neuronal death in primarily cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/R) in rats. Oral administration of ACG (10, 25, and 50 mg/kg) 30 min before MCAO, after 1 h of MCAO, and after 1 h of reperfusion reduced MCAO/R-induced brain infarct and edema formation. ACG also inhibited development of behavioral disabilities in MCAO/R-treated rats. Exposure of cultured cortical neurons to 500 μM glutamate for 12 h resulted in neuronal cell death. ACG (1, 10, and 50 μg/mL) inhibited glutamate-induced neuronal death. Furthermore, ACG inhibited 100 μM hydrogen peroxide (H2O2)- and hypoxia-induced neuronal death. These results suggest that the neuroprotective effect of ACG against ischemia-induced brain damage might be associated with its anti-excitotoxic and anti-oxidative activity and that ACG may have a therapeutic role for prevention of neurodegeneration in stroke.