Abstract
Improving and maintaining memory function is effective in preventing cognitive decline and dementia. Previously, we demonstrated that iso-α-acids, the hop-derived bitter components in beer, prevent cognitive impairment in an Alzheimer’s disease mouse model. In this report, we investigated the effects of matured hop bitter acids (MHBA) containing components of oxides derived from α- and β-acids, and structurally similar to iso-α-acids, on cognitive function using behavioral pharmacological procedures. MHBA and the representative components of MHBA, 4′-hydroxyallohumulinone (HAH) and 4′-hydroxy-cis-alloisohumulone (HAIH) improved spatial working memory in scopolamine-induced amnesia mice. MHBA also enhanced episodic memory in the novel object recognition test (NORT). The administration of MHBA increased the amount of norepinephrine (NE) and NE release into cerebrospinal fluid (CSF) in hippocampus. The MHBA activity in improving memory function was attenuated by treatment with a β-adrenergic receptor inhibitor. In addition, vagotomized mice did not display the memory improvement induced by MHBA. Together, our results suggest that MHBA improves memory function via stimulation of the vagus nerve and enhancement of NE release in the hippocampus. Vagus nerve activation by the intake of food materials including MHBA may be a safe and effective approach for improving cognitive function.
Highlights
Several acetylcholinesterase (AChE) inhibitors have been reported to enhance spontaneous alternation in scopolamine-induced amnesia[31,32], but matured hop bitter acids (MHBA) exhibited no effects on the AChE activity
The vagus nerve is considered to be a therapeutic target for several central nervous system (CNS) disorders including dementia and cognitive decline[28]
Results of the present study suggest that stimulation of the vagus nerve by food materials may be an effective and safe approach for treating cognitive impairment or dementia, because they influence brain function without penetrating the blood-brain barrier
Summary
Our group previously demonstrated that iso-α-acids prevent lipid accumulation and insulin resistance in diet-induced obese rodents[13,14,15] and improve glucose metabolism and body fat accumulation in a clinical trial[16]. The α- and β-acids are converted to oxidized components called matured hop bitter acids (MHBA) that contain a β-tricarbonyl formula and a common chemical structure with iso-α-acids[17,18,19] Because of their structural similarity to iso-α-acids, MHBA are expected to have similar physiological effects as those of iso-α-acids, such as preventing obesity and cognitive impairment. MHBA may improve cognitive function through vagus nerve stimulation. We investigated the effects of MHBA on cognitive function in young normal adult mice and scopolamine-induced amnesia model mice, using behavioral pharmacological methods.
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