BRAIN and NERVE－神経研究の進歩74巻8号

2022年08月発行

特集 迷走神経の不思議

ホップ由来苦味酸による脳腸相関活性化—食成分を通じた迷走神経刺激

著者： 阿野泰久¹

所属機関： ¹キリンホールディングス株式会社R＆D本部キリン中央研究所

ページ範囲：P.1003 - P.1009

文献概要

超高齢社会や社会環境変化により認知機能や気分状態の維持改善が重要な社会課題となっている。ビールの苦味成分としても知られるホップ由来苦味酸が，腸の苦味受容体に作用し，迷走神経を刺激することで脳腸相関の活性化により認知機能および抑うつ状態を改善することが非臨床試験で確認され，健常中高齢者対象の臨床試験でも有効性が確認されている。食を通じた迷走神経刺激は日常的に続けやすく，新たな予防方法の開発が期待される。

参考文献

1）総務省統計局：人口推計　https://www.stat.go.jp/data/jinsui/index.html（最終閲覧日：2022年6月2日）

2）内閣府：平成29年版高齢社会白書（全体版）　https://www8.cao.go.jp/kourei/whitepaper/w-2017/zenbun/29pdf_index.html（最終閲覧日：2022年6月2日）

3）Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, et al: Alzheimer's disease. Lancet 388: 505-517, 2016

4）Thal DR, Attems J, Ewers M: Spreading of amyloid, tau, and microvascular pathology in Alzheimer's disease: findings from neuropathological and neuroimaging studies. J Alzheimers Dis 42 Suppl 4: S421-S429, 2014

5）Cederholm T, Salem N Jr, Palmblad J: ω-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr 4: 672-676, 2013

6）Hamaguchi T, Ono K, Yamada M: Review: curcumin and Alzheimer's disease. CNS Neurosci Ther 16: 285-297, 2010

7）Albarracin SL, Stab B, Casas Z, Sutachan JJ, Samudio I, et al: Effects of natural antioxidants in neurodegenerative disease. Nutr Neurosci 15: 1-9, 2012

8）Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM, et al: Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet 359: 281-286, 2002

9）Horvat P, Richards M, Kubinova R, Pajak A, Malyutina S, et al: Alcohol consumption, drinking patterns, and cognitive function in older Eastern European adults. Neurology 84: 287-295, 2015

10）Arntzen KA, Schirmer H, Wilsgaard T, Mathiesen EB: Moderate wine consumption is associated with better cognitive test results: a 7 year follow up of 5033 subjects in the Tromsø Study. Acta Neurol Scand 122(Suppl.190): 23-29, 2010

11）Gu J, Li Z, Chen H, Xu X, Li Y, et al: Neuroprotective effect of trans-resveratrol in mild to moderate Alzheimer disease: a randomized, double-blind trial. Neurol Ther 10: 905-917, 2021

12）Vidavalur R, Otani H, Singal PK, Maulik N: Significance of wine and resveratrol in cardiovascular disease: French paradox revisited. Exp Clin Cardiol 11: 217-225, 2006

13）Ayabe T, Fukuda T, Ano Y: Improving effects of hop-derived bitter acids in beer on cognitive functions: a new strategy for vagus nerve stimulation. Biomolecules 10:131, 2020［doi: 10.3390/biom10010131］

14）Taniguchi Y, Matsukura Y, Ozaki H, Nishimura K, Shindo K: Identification and quantification of the oxidation products derived from α-acids and beta-acids during storage of hops (Humulus lupulus L.). J Agric Food Chem 61: 3121-3130, 2013

15）Obara K, Mizutani M, Hitomi Y, Yajima H, Kondo K: Isohumulones, the bitter component of beer, improve hyperglycemia and decrease body fat in Japanese subjects with prediabetes. Clin Nutr 28: 278-284, 2009

16）Morimoto-Kobayashi Y, Ohara K, Ashigai H, Kanaya T, Koizumi K, et al: Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study. Nutr J 15: 25, 2016

17）Ano Y, Hoshi A, Ayabe T, Ohya R, Uchida S, et al: Iso-alpha-acids, the bitter components of beer, improve hippocampus-dependent memory through vagus nerve activation. FASEB J 33: 4987-4995, 2019

18）Ayabe T, Ohya R, Taniguchi Y, Shindo K, Kondo K, et al: Matured hop-derived bitter components in beer improve hippocampus-dependent memory through activation of the vagus nerve. Sci Rep 8: 15372, 2018［doi: 10.1038/s41598-018-33866-1］

19）Fukuda T, Ayabe T, Ohya R, Ano Y: Matured hop bitter acids improve spatial working and object recognition memory via nicotinic acetylcholine receptors. Psychopharmacology (Berl) 236: 2847-2854, 2019

20）Yamazaki T, Morimoto-Kobayashi Y, Koizumi K, Takahashi C, Nakajima S, et al: Secretion of a gastrointestinal hormone, cholecystokinin, by hop-derived bitter components activates sympathetic nerves in brown adipose tissue. J Nutr Biochem 64: 80-87, 2019

21）Yamazaki T, Takahashi C, Taniguchi Y, Narukawa M, Misaka T, et al: Bitter taste receptor activation by hop-derived bitter components induces gastrointestinal hormone production in enteroendocrine cells. Biochem Biophys Res Commun 533: 704-709, 2020

22）Fukuda T, Ohya R, Kobayashi K, Ano Y: Matured hop bitter acids in beer improve lipopolysaccharide-induced depression-like behavior. Front Neurosci 13: 41, 2019［doi: 10.3389/fnins.2019.00041］

23）Ano Y, Dohata A, Taniguchi Y, Hoshi A, Uchida K, et al: Iso-α-acids, bitter components of beer, prevent inflammation and cognitive decline induced in a mouse model of Alzheimer's disease. J Biol Chem 292: 3720-3728, 2017

24）Ano Y, Ohya R, Yamazaki T, Takahashi C, Taniguchi Y, et al: Hop bitter acids containing a β-carbonyl moiety prevent inflammation-induced cognitive decline via the vagus nerve and noradrenergic system. Sci Rep 10: 20028, 2020［doi: 10.1038/s41598-020-77034-w］

25）Fukuda T, Obara K, Saito J, Umeda S, Ano Y: Effects of hop bitter acids, bitter components in beer, on cognition in healthy adults: a randomized controlled trial. J Agric Food Chem 68: 206-212, 2020

26）Fukuda T, Ohnuma T, Obara K, Kondo S, Arai H, et al: Supplementation with matured hop bitter acids improves cognitive performance and mood state in healthy older adults with subjective cognitive decline. J Alzheimers Dis 76: 387-398, 2020