Aralia cordata Protects Against Amyloid β Protein (25–35)–Induced Neurotoxicity in Cultured Neurons and Has Antidementia Activities in Mice

Abstract

The present study investigated an ethanol extract of the aerial part of Aralia cordata Thunb. (Araliaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid β (Aβ) protein (25 – 35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to 10 μM Aβ(25 – 35) for 36 h induced neuronal apoptotic death. At 1 – 10 μg/ml, A. cordata inhibited neuronal death, elevation of intracellular calcium ([Ca2+]i), glutamate release into the medium, and generation of reactive oxygen species (ROS) induced by Aβ(25–35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol Aβ(25–35) was inhibited by chronic treatment with A. cordata (50 and 100 mg/kg, p.o. for 7 days) as measured by a passive avoidance test, and corresponding reductions were observed in brain cholinesterase activity and neuronal death measured histologically in the hippocampal region. Oleanolic acid isolated from A. cordata also inhibited neuronal death, elevation of [Ca2+]i, glutamate release, and generation of ROS induced by Aβ(25–35) in cultured rat cortical neurons, suggesting that the neuroprotective effect of A. cordata may be, at least in part, attributable to this compound. From these results, we suggest that the antidementia effect of A. cordata is due to its neuroprotective effect against Aβ(25–35)-induced neurotoxicity and that A. cordata may have a therapeutic role in preventing the progression of Alzheimer’s disease. Keywords:: Aralia cordata, oleanolic acid, amyloid β protein, cultured neuronal death, memory impairment