Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease

Abstract

Edited by Luke O'NeillAlongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-␣-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor ␥. In normal mice, oral administration of iso-␣-acids led to a significant increase both in CD11b and CD206 doublepositive anti-inflammatory type microglia (p < 0.05) and in microglial phagocytosis in the brain. In Alzheimer's model 5xFAD mice, oral administration of iso-␣-acids resulted in a 21% reduction in amyloid ␤ in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1␤ and chemokines including macrophage inflammatory protein-1␣ in the cerebral cortex (p < 0.05) and a significant improvement in a novel object recognition test (p < 0.05), as compared with control-fed 5xFAD mice. The differences in iso-␣-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid ␤ deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-␣-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-␣-acids contained in beer may be useful for the prevention of dementia.

Innovative beer-brewing of typical, old and healthy wheat varieties to boost their spreading

“…Specific and significant preventive action against Alzheimer disease from hops' iso-α-acids, which are responsible for bitterness in beer, was recently argued along with its potentially deep social impact with rapidly ageing populations worldwide (Ano et al, 2017). Moreover, evidence has arisen for anti-carcinogenic action from hops' prenil-flavonoids (Ferk et al, 2010;Karabin et al, 2015; Ż ołnierczyk et al, 2015), as well as from phenolic constituents extracted from both malt and hop (Ferk et al, 2010;Gerhäuser, 2005).…”

Beer produced via hydrodynamic cavitation retains higher amounts of xanthohumol and other hops prenylflavonoids

“…Among other substances, hop's iso-α-acids were recently attributed specific and significant preventive action against the Alzheimer disease (Ano et al, 2017), as well as beer was estimated as one of the richest sources of silicon in the diet, which is important for the growth and development of bone and connective tissue (Casey & Bamforth, 2010).…”

Bitter Components in Beer Regulate Microglial Inflammation and Prevent Cognitive Decline

“…On the other hand, even though it is the most-consumed alcoholic beverage, no constituents of beer had been demonstrated to have preventive effects on dementia. However, a recent study using a rodent model has now shown that intake of ingredients in beer has preventive effects on Alzheimer's disease pathology [9]. These ingredients are iso-α-acids, the hop-derived bitter components of beer.…”

“…More recently, iso-α-acids were identified as novel components regulating microglia [9], a type of immune cell in the nervous systems. As a regulator of the immune response in the brain, microglia have been recently attracting increasing attention because numerous reports suggest that inflammation in the brain severely induces cognitive decline and exacerbates Alzheimer's disease pathology.…”

“…Microglia play an important role in removing waste products such as Aβ, but their function declines alongside the aging process, when, in contrast, they can induce inflammation in the brain. Iso-α-acids were identified as a component in beer that can enhance microglial phagocytic activity (Figure 2A and 2B) and suppress microglial inflammatory responses [9]. Iso-α-acids enhanced both microglial phagocytosis of Aβ and expression of CD36, a scavenger receptor for Aβ ( Figure 2C) [12].…”