title: Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property.
abstract: 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 10mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in the several behavioral tasks. Also, single administration of swertisin (10mg/kg, p.o.) in normal naïve 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, 0.1mg/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 (PKA, 5 or 10mg/kg) and CREB (10mg/kg), and co-administration of CPA (0.1mg/kg, i.p) blocked the increased phosphorylated levels of PKA 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.
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jeon
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Byeol
authors.initials: B
authors.lastname: Ryu
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Younghwan
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Haneul
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea. Electronic address: dsjang@khu.ac.kr.
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Oriental Pharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D016466:CHO Cells; D050882:CREB-Binding Protein / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000633:toxicity; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D011485:Protein Binding / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D012153:Retention, Psychology / Q000187:drug effects; D012601:Scopolamine / Q000633:toxicity
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D018680:Cholinergic Antagonists; D058906:Purinergic P1 Receptor Agonists; C556941:swertisin; C048599:N(6)-cyclopentyladenosine; D047310:Apigenin; D012601:Scopolamine; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine
keywords: Adenosine; Alzheimer’s disease; Memory impairment; Swertisin