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Int. J. Mol. Sci. 2017, 18(3), 489; doi:10.3390/ijms18030489

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
Received: 26 December 2016 / Revised: 20 February 2017 / Accepted: 20 February 2017 / Published: 24 February 2017
View Full-Text   |   Download PDF [2548 KB, uploaded 24 February 2017]   |  

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. 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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