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Open AccessArticle

Permeation of Polymethoxyflavones into the Mouse Brain and Their Effect on MK-801-Induced Locomotive Hyperactivity

1
Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan
2
Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: David Arráez-Román and Ana Maria Gómez Caravaca
Int. J. Mol. Sci. 2017, 18(3), 489; https://doi.org/10.3390/ijms18030489
Received: 26 December 2016 / Revised: 20 February 2017 / Accepted: 20 February 2017 / Published: 24 February 2017
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. View Full-Text
Keywords: polymethoxyflavone; heptamethoxyflavone; nobiletin; tangeretin; natsudaidain; blood-brain-barrier; locomotive hyperactivity; ERK1/2; MK-801 polymethoxyflavone; heptamethoxyflavone; nobiletin; tangeretin; natsudaidain; blood-brain-barrier; locomotive hyperactivity; ERK1/2; MK-801
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Okuyama, S.; Miyazaki, K.; Yamada, R.; Amakura, Y.; Yoshimura, M.; Sawamoto, A.; Nakajima, M.; Furukawa, Y. Permeation of Polymethoxyflavones into the Mouse Brain and Their Effect on MK-801-Induced Locomotive Hyperactivity. Int. J. Mol. Sci. 2017, 18, 489.

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