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

Alongside 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 double-positive 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.