title: Physiological effects of hop and barley derived beer components
Creators: name: Li, Yan
Publisher: name: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Year: 2024
Subjects: subject: antibacterial activity; locomotor activity; alcohol addiction
subject: DDC Classification::5 Naturwissenschaften und Mathematik :: 54 Chemie :: 540 Chemie und zugeordnete Wissenschaften

description: Beer is an alcoholic beverage produced from four major raw ingredients including hop, barley, yeast, and water. The phytochemicals of the raw ingredients contribute to the quality of beer and to human health. In the first part of this work, the two complementary untargeted methods, activity-guided fractionation and metabolome profiling, were used to systematically determine the main molecular contributor to the antibacterial activity of hop in an unbiased way. After using both approaches to obtain the most active components, the purified antibacterial components and their concentrations were also thought to influence the overall antibacterial effect of hop. On the one hand, MIC and MBC assays were used to screen for active hop varieties, fractions, and single components in vitro. The ethanolic extracts of five hop varieties for beer brewing showed significant antibacterial activity, but no antibacterial activity was observed in the tea hop sample. Afterwards, the molecular structures of the antibacterial components in the most active hop variety were determined. Activity-guided fractionation thus suggests that lupulones, humulones, and xanthohumol play a determinant role in the antibacterial property of the hop extract. On the other hand, untargeted LC–timsTOF-MS/MS-based metabolomics was conducted to screen for possible antibacterial metabolites, followed by a series of multivariate and univariate statistical analyses. After metabolome analysis, colupulone, lupulone, adlupulone, humulone, and adhumulone were identified as antibacterial constituents among numerous hop metabolites. The results of metabolome profiling were ultimately in good agreement with those of activity-guided fractionation, which can serve as a complementary approach to identify the antibacterial components of the hop extract. Finally, to determine the contribution of single hop components to the overall antibacterial activity of the hop extract, the concentrations of xanthohumol, humulone congeners (cohumulone, humulone, and adhumulone), and lupulone congeners (colupulone, lupulone, and adlupulone) were quantified and their antibacterial activity values were also calculated accordingly. The antibacterial activity value indicated that the antibacterial effect of the hop extract was mainly attributed to colupulone and lupulone. The results of two complementary untargeted approaches also showed that these two compounds were the main contributors to the antibacterial activity of the hop extract. In the second part of this work, the effect of the beer component hordenine on anxiety-related behaviors in mice was assessed using an open field (OF) apparatus. The OF test is frequently used to measure emotional states such as anxiogenic and anxiolytic effects. The results of OF test indicated that hordenine reduced locomotor activity in mice with an apparent dose-dependent response after treatment with four doses of hordenine (1, 5, 25, and 50 mg/kg). The reduced time spent in the center of the OF arena is probably due to the sedative effect of hordenine. There has been a long-standing interest in the use of stress- and anxiety-related substances as an option for the treatment of alcohol addiction. In this sense, we proposed a hypothesis that hordenine may be able to modulate alcohol consumption. A two-bottle free-choice paradigm was therefore used to develop new candidates for the treatment of acute alcohol use and relapse. In general, relapse to alcohol is the major clinical issue in the treatment of alcohol addiction. In this procedure, three hordenine treatment episodes were delivered to mice at three stages including treatment during acute alcohol drinking, treatment before alcohol relapse, and treatment during relapse. In conclusion, hordenine attenuated alcohol consumption when treatment was administered during acute drinking or before relapse. However, hordenine treatment during relapse did not significantly reduce alcohol consumption in mice when they resumed drinking. Overall, these observations suggest that hordenine could be a therapeutic or prophylactic agent for alcohol addiction at an early stage. Next, an alcohol-induced conditioned place preference (CPP) test was used to ascertain the effect of hordenine on the rewarding properties of alcohol by measuring preference for an associated place. Hordenine had the potential to retrieve conditioned alcohol effects and showed a significant dose-dependent response in the reduction of locomotion. The findings regarding the sedative effects of hordenine were consistent with the OF test. In the last part of this work, the neurobiological mechanisms of hordenine on alcohol-addiction associated behaviors were revealed. Hordenine is effective in limiting alcohol consumption in mice and could be a potential candidate for treating alcohol addiction at an early stage. Dysfunction of the monoaminergic system is implicated in alcohol use disorder. Monoamine levels were altered in the brains of mice after chronic hordenine treatments. Hordenine significantly increased the concentrations of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) in different brain regions. We can speculate that changes in monoamine concentrations may be associated with the suppression of acute alcohol consumption and relapse prevention. In general, monoamine transporters are critical molecular targets that mediate abuse-related effects of psychostimulants such as alcohol and cocaine. The current work concludes that hordenine exhibits micromolar affinity to the human serotonin transporter (SERT) and dopamine transporter (DAT), which is probably related to serotoninergic and dopaminergic signaling. The effects of hordenine on the monoaminergic system provide new insights into possible mechanisms of hordenine on the reduction of alcohol consumption. Additionally, LC–MS/MS analysis revealed the presence of small amounts of hordenine in the brains of mice, although the mice were not treated with hordenine. There was no difference in the content of hordenine in the brains of mice between the vehicle and hordenine-treated groups two hours after the last administration.