Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

Aims: Learning and memory impairment is a common symptom in the early stages of various types of dementia. It is likely to reduce the incidence of dementia with correct intervention. alpha-Asarone is the main bioactive substance isolated from Acorus tatarinowii Schott and has been proven to improve memory dysfunction; however, at present, the specific underlying mechanism is poorly understood. The aim of the present study was to investigate the effect of alpha-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. Main methods: A mouse model of impaired learning and memory was created by ethanol (2.0 g/kg, i.g.). alpha-Asarone (7.5, 15 or 30 mg/kg, i.p.) was delivered 10 min prior to ethanol administration. The behavioral effect of alpha-asarone was evaluated using the novel object recognition test. Glutamate (Glu) and gamma-aminobutyric acid (GABA) levels in the hippocampus were determined by ELISA, and the protein expression levels of hippocampal GluR2, NMDAR2B, SYNI, GLT-1 and CaMK. were detected by western blotting. Key findings: Pretreatment with alpha-asarone significantly improved the behavioral performance, regulated the imbalance of Glu and GABA in the hippocampus and the abnormal expression of related proteins. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu. Significance: Our results show that the improvement in learning and memory elicited by alpha-asarone may providing a possible novel candidate for the prevention of learning and memory impairment in the early stages of dementia.