The ameliorating effects of 5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one, an oroxylin A derivative, against memory impairment and sensorimotor gating deficit in mice |
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Authors: | Xiaotong Liu Sung In Hong Se Jin Park June Bryan dela Peña Haiyan Che Seo Young Yoon Dong Hyun Kim Jong Min Kim Mudan Cai Victoria Risbrough Mark A. Geyer Chan Young Shin Jae Hoon Cheong Haeil Park Jae Hwan Lew Jong Hoon Ryu |
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Affiliation: | 1. Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, 130-701, Republic of Korea 3. Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Republic of Korea 8. Department of East-West Integrated Medicine, Kyung Hee University Medical Center, Seoul, 130-702, South Korea 5. Department of Pharmacy, Sahmyook University, Seoul, 139-742, Republic of Korea 4. College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Republic of Korea 7. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA 6. Department of Pharmacology, School of Medicine, Konkuk University, Seoul, 143-701, Republic of Korea 9. Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si, Gyeonggi-do, 446-701, South Korea 2. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Republic of Korea
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Abstract: | We previously reported that oroxylin A, a γ-aminobutyric acid A (GABAA) receptor antagonist, ameliorates drugs-induced memory impairments. We synthesized several oroxylin A derivatives in efforts to find a substance that has pro-cognitive effects as well as improves sensorimotor gating. The aim of the present study is to investigate the effect of a novel oroxylin A derivative, 5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on pharmacological models of schizophrenia, which exhibit memory impairment and sensorimotor gating deficit. Memory impairment was induced by scopolamine, a muscarinic receptor antagonist, or MK-801, an N-methyl-d-aspartate receptor antagonist. Sensorimotor gating deficits were induced by MK-801 and measured by prepulse inhibition (PPI) of the acoustic startle response task. DMPC treatment (20 mg/kg) significantly attenuated scopolamine- or MK-801-induced memory impairment and it even enhanced cognitive performance of normal animals. Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the acoustic startle response task. In an in vitro study, DMPC (20 μM) inhibited intracellular Cl? influx induced by muscimol, a selective GABAA receptor agonist. These results suggest that DMPC would be a potential candidate for alleviating cognitive dysfunction and sensorimotor gating deficits in schizophrenia, and that its effects may be mediated, in part, via blockade of the GABAergic neurotransmitter system. |
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