Iso-α-Acids, the Bitter Components of Beer, Suppress Microglial Inflammation in rTg4510 Tauopathy.

Yasuhisa Ano,Keiji Kondo,Hiroyuki Nakayama,Yuta Takaichi,Akihiko Takashima,Kazuyuki Uchida

doi:10.3390/molecules23123133

Abstract

Due to the growth in aging populations, prevention for cognitive decline and dementia are in great demand. We previously demonstrated that the consumption of iso-α-acids (IAA), the hop-derived bitter compounds in beer, prevents inflammation and Alzheimer’s disease pathology in model mice. However, the effects of iso-α-acids on inflammation induced by other agents aside from amyloid β have not been investigated. In this study, we demonstrated that the consumption of iso-α-acids suppressed microglial inflammation in the frontal cortex of rTg4510 tauopathy mice. In addition, the levels of inflammatory cytokines and chemokines, including IL-1β and MIP-1β, in the frontal cortex of rTg4510 mice were greater than those of wild-type mice, and were reduced in rTg4510 mice fed with iso-α-acids. Flow cytometry analysis demonstrated that the expression of cells producing CD86, CD68, TSPO, MIP-1α, TNF-α, and IL-1β in microglia was increased in rTg4510 mice compared with wild-type mice. Furthermore, the expression of CD86- and MIP-1α-producing cells was reduced in rTg4510 mice administered with iso-α-acids. Moreover, the consumption of iso-α-acids reduced the levels of phosphorylated tau in the frontal cortex. Collectively, these results suggest that the consumption of iso-α-acids prevents the inflammation induced in tauopathy mice. Thus, iso-α-acids may help in preventing inflammation-related brain disorders.

Highlights

Dementia and cognitive impairment are becoming an increasing burden on patients and their families, and on national healthcare systems worldwide, concomitant with the rapid growth in aging populations
To evaluate the effects of iso-α-acids on inflammation in the brain of rTg4510 tauopathy mice, the levels of proinflammatory cytokines and chemokines in the frontal cortex of tauopathy mice fed with iso-α-acids were measured
These results indicate that proinflammatory cytokines and chemokines are increased in the frontal cortex in rTg4510 mice, and the consumption of iso-α-acids reduce the inflammation induced in tauopathy mice

Summary

Introduction

Dementia and cognitive impairment are becoming an increasing burden on patients and their families, and on national healthcare systems worldwide, concomitant with the rapid growth in aging populations. Owing to the lack of disease-modifying therapies for dementia, preventive approaches, including diet, exercise, and learning are garnering increased attention. Etiological studies of lifestyle have demonstrated that low-to-moderate consumption of alcohol, such as wine and beer, may reduce the risk of cognitive decline and the development of dementia. Individuals who consume low-to-moderate levels of alcoholic beverages on a daily basis were shown to have a significantly lower risk of developing a neurodegenerative disease, as compared with individuals who abstained from alcohol beverages or drank heavily [1,2,3]. Apart from the effects of alcohol itself, resveratrol, a polyphenolic compound present in red wine, has been shown to be Molecules 2018, 23, 3133; doi:10.3390/molecules23123133 www.mdpi.com/journal/molecules. We previously demonstrated that the consumption of iso-α-acids, the bitter components present in beer, prevents Alzheimer’s pathology in 5 × FAD transgenic model mice

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