Improvement of Impaired Memory in Mice by Schisandrin

摘要

We assessed the effectiveness and mechanism of action of schisandrin on modulation of learning and memory disorders in mice. Memory impairment was established in mice by intraperitoneal injection of pentobarbital sodium (20 mg/kg) . Schisandrin (0.5, 1.0, 2.0g/kg) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of schisandrin to reduce phenobarbital-induced learning and memory impairment. The levels of superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT) were measured in brain tissue samples taken from the mice. Other biomarkers measured included expression of nuclear transcription factor-kappa-B (NF-kB) and brain-derived neurotrophic factor (BDNF) in the hippocampus CAl region, which were determined by immunohistochemical analysis. On the fifth day of treatment, the mice in the pentobarbital sodium group performed worse on the Morris water maze test compared to untreated controls (P<0.01), which could be prolonged after schisandrin treatment (P<0.05 for low and intermediate dose groups). Analysis of brain tissues showed that, compared with the control group, NO levels were increased and SOD, CAT activity decreased in the pentobarbital sodium group (P<0.01). After treatment with schisandrin, the NO levels were significantly decreased (P<0.01), while SOD and CAT activity increased (P<0.01). Immunohistochemistry analysis showed that, in phenobarbital only group, the protein expression of BDNF decreased, NF-kB increased compared to untreated controls, and schisandrin could reverse this trend (P<0.05 and P<0.01, respectively) . The results suggest that schisandrin is effective in improving the learning and memory deficiency induced by pentobarbital sodium, the mechanism of which may be related modulation of cellular response to oxidative stress.