title: Permeation of Polymethoxyflavones into the Mouse Brain and Their Effect on MK-801-Induced Locomotive Hyperactivity.
abstract: Accumulating data have indicated that citrus polymethoxyflavones (PMFs) have the ability to affect brain function. In the present study, we showed that 3,5,6,7,8,3',4'-heptamethoxy- flavone (HMF) given intraperitoneally to mice was immediately detected in the brain and that the permeability of the brain tissues to it was significantly higher than that of other citrus PMFs (nobiletin, tangeretin, and natsudaidain). The permeation of these PMFs into the brain well correlated with their abilities to suppress MK-801-induced locomotive hyperactivity, suggesting that HMF had the ability to act directly in the brain. We also obtained data suggesting that the suppressive effect of HMF on MK-801-induced locomotive hyperactivity was mediated by phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the hippocampus.
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. sokuyama@cc.matsuyama-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okuyama
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. mu.yakuri.002@gmail.com.
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 46150023@cc.matsuyama-u.ac.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. amakura@cc.matsuyama-u.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Amakura
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. myoshimu@cc.matsuyama-u.ac.jp.
authors.forename: Morio
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 46140018@cc.matsuyama-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawamoto
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. mnakajim@cc.matsuyama-u.ac.jp.
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. furukawa@cc.matsuyama-u.ac.jp.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry; D016291:Dizocilpine Maleate / Q000009:adverse effects*; D047309:Flavones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy; D007274:Injections, Intraperitoneal; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D010539:Permeability; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047309:Flavones; D010936:Plant Extracts; D016291:Dizocilpine Maleate
keywords: ERK1/2; MK-801; blood-brain-barrier; heptamethoxyflavone; locomotive hyperactivity; natsudaidain; nobiletin; polymethoxyflavone; tangeretin