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Title: Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.
Authors: Sasaoka, Norio  kyouindb  KAKEN_id
Sakamoto, Megumi
Kanemori, Shoko
Kan, Michiru
Tsukano, Chihiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Takemoto, Yoshiji  kyouindb  KAKEN_id  orcid (unconfirmed)
Kakizuka, Akira  kyouindb  KAKEN_id
Author's alias: 垣塚, 彰
Issue Date: 29-Jan-2014
Publisher: Public Library of Science
Journal title: PloS one
Volume: 9
Issue: 1
Thesis number: e87185
Abstract: Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.
Description: ホップ抽出物でアルツハイマー病の発症を抑えることに成功 -認知症の発症と進行の予防につながると期待-. 京都大学プレスリリース. 2014-01-30.
Rights: © 2014 Sasaoka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pone.0087185
PubMed ID: 24489866
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