Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property

초록

Swertisin, a C-glucosylflavone isolated from Swertia japonica, has been known to have anti-inflammatory or antidiabetic activities. Until yet, however, its cognitive function is not investigated. In the present study, we endeavored to elucidate the effects of swertisin on cholinergic blockade-induced memory impairment. Swertisin (5 or 10 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in the several behavioral tasks. Also, single administration of swertisin (10 mg/kg, p.o.) in normal naive mice enhanced the latency time in the passive avoidance task. In addition, the ameliorating effect of swertisin on scopolamine-induced memory impairment was significantly antagonized by a sub effective dose of N6-cyclopentyladenosine (CPA, 0.1 mg/kg, i.p). The adenosine A1 receptor antagonistic property of swertisin was confirmed by receptor binding assay. Furthermore, the administration of swertisin significantly increased the phosphorylation levels of hippocampal or cortical protein kinase A (PICA, 5 or 10 mg/kg) and CREB (10 mg/kg), and co-administration of CPA (0.1 mg/kg, i.p) blocked the increased phosphorylated levels of PICA and CREB in the both cortex and hippocampus. Taken together, these results indicate that the memory-ameliorating effects of swertisin may be, in part, mediated through the adenosinergic neurotransmitter system, and that swertisin may be useful for the treatment of cognitive dysfunction observed in several diseases such as Alzheimer's disease. (C) 2016 Elsevier B.V. All rights reserved.

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