, Volume 236, Issue 9, pp 2847–2854 | Cite as

Matured hop bitter acids improve spatial working and object recognition memory via nicotinic acetylcholine receptors

  • Takafumi FukudaEmail author
  • Tatsuhiro Ayabe
  • Rena Ohya
  • Yasuhisa Ano
Original Investigation



Cognitive decline and dementia are major concerns in today’s aging society. As limited treatments are available, measures to prevent cognitive decline and dementia are needed. We previously demonstrated that matured hop bitter acids (MHBA), bitter components of beer, increase norepinephrine in the hippocampus and improve memory in amnesia model mice induced by scopolamine (SCP), an antagonist of muscarinic receptor. However, other neurotransmitters involved in the effects of MHBA on memory improvement remain unknown.


This study aimed to assess the role of acetylcholine receptors (AChR) in the effects of MHBA on memory.


The involvement of AChR on the effects of MHBA (10 mg/kg) on cognitive function was evaluated using AChR antagonists, SCP, mecamylamine hydrochloride (MEC), a non-competitive antagonist of nicotinic-AChR (nAChR), and methyllycaconitine citrate (MLA), an α7nAChR antagonist, for the Y-maze test and the novel object recognition test (NORT). A separate population of mice, which underwent vagotomy or sham operation, was subjected to NORT to elucidate further mechanism. In addition, the effect of MHBA on acetylcholinesterase (AChE) activity was measured in vitro.


In accordance with previous reports, MHBA improved spontaneous alternations of the Y-maze test in SCP-induced amnesia mice and increased discrimination index evaluated by the NORT in normal mice. On the other hand, treatment with MEC or MLA attenuated the effects of MHBA on memory improvement in the Y-maze test and the NORT. Vagotomized mice also showed attenuated memory enhancement by MHBA in the NORT. In addition, MHBA did not alter AChE activity in vitro.


The results support the involvement of nAChRs in memory improvement in mice by MHBA. MHBA is thus thought to activate the vagal nerve and enhance hippocampus-dependent memory via nAChRs.


Matured hop bitter acids Memory Cognition Acetylcholine α7-nicotinic acetylcholine receptor 



We thank Dr. Yoshimasa Taniguchi of Central Laboratories for Key Technologies, Kirin Co., Ltd., for kindly providing us MHBA.

Compliance with ethical standards

Competing interests

All of the authors are employees of Kirin Company, Ltd. The authors declare no other conflict of interest associated with this study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Takafumi Fukuda
    • 1
    Email author
  • Tatsuhiro Ayabe
    • 1
  • Rena Ohya
    • 1
  • Yasuhisa Ano
    • 1
  1. 1.Research Laboratories for Health Science & Food TechnologiesKirin Company, Ltd.YokohamaJapan

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