Matured Hop Bitter Acids in Beer Improve Lipopolysaccharide-Induced Depression-Like Behavior

Recent studies have demonstrated a close association between neural inflammation and development of mental illnesses, such as depression. Clinical trials have reported that treatment with non-steroidal anti-inflammatory drugs is associated with reduced risk of depression. Moreover, nutritional approaches for the prevention and management of depression have garnered significant attention in recent years. We have previously demonstrated that iso-alpha-acids (IAAs)-the bitter components in beer- suppress hippocampal microglial inflammation, thereby improving cognitive decline. However, effects of hop-derived components other than IAAs on inflammation have not been elucidated. In the present study, we demonstrated that consumption of matured hop bitter acids (MHBAs) generated from alpha- and beta-acids, which show a high similarity with the chemical structure of IAAs, suppress lipopolysaccharide (LPS)-induced cytokine productions in the brain. MHBAs administration increased norepinephrine (NE) secretion and reduced immobility time which represents depression-like behavior in the tail suspension test. Moreover, MHBAs components, including hydroxyallohumulinones and hydroxyalloisohumulones, reduced LPS-induced immobility time. Although further researches are needed to clarify the underlying mechanisms, these findings suggest that MHBAs reduce inflammatory cytokine productions and increase NE secretion, thereby improving depression-like behavior. Similarly, inoculation with LPS induced loss of dendritic spines, which was improved upon MHBAs administration. Additionally, vagotomized mice showed attenuated improvement of immobility time, increase in NE level, and improvement of dendrite spine density following MHBAs administration. Therefore, MHBAs activate the vagus nerve and suppress neuronal damage and depression-like behavior induced by inflammation.