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To investigate the chemical and sensorial impact of dry hopping time on typical pale ale, a standardized beer was produced and separated into ten vessels. Nine vessels were dry hopped, and one vessel remained un-hopped as a control. Impact of dry hopping contact time was investigated over 96 h. Polyphenols and iso-α-acid t/c ratio were analyzed in both Young and Aged beer samples. Total polyphenol content generally increased in both young and aged treatments compared to controls. Analysis of the t/c ratio suggests that both Young and Aged beers were chemically preserved to some degree after approximately 12 h at the given dry hopping rate regardless of age. Within the Aged beer trials, 96 h of dry hop contact yielded a significant increase in t/c ratio compared to all other Aged trials. This suggests that a 4-day dry hop regime may yield additional oxidative protection of iso-α-acids in beers stored unrefrigerated for 30 days. Descriptive analysis was also performed with an 8-person, trained panel; however, beers were sensorially distinguished by their aging time as opposed to their dry hopping time.

This paper investigates the binding behavior of iso-α-acids from hops on free wort amino acids and proteins concerning the wort production process in breweries. The studies were carried out with different amino acids, bovine serum albumin and wort. To identify the nature of reaction between iso-α-acids and these substances, analyses of free amino nitrogen, HPLC and isothermal titration calorimetry were performed. According to the results, the iso-α-acids do not form covalent bonds with free amino acids of wort. However, iso-α-acids, especially isohumulone and isoadhumulone, form ionic bonds with wort proteins. A distinction must be made between proteins that are present in the hot trub, and those that are still dissolved in the hot wort. Proteins that are already coagulated and precipitated no longer react with iso-α-acids. Future experiments will investigate whether the established ionic bonds between iso-α-acids and proteins from the wort preparation process are maintained during fermentation until the finished beer or beer foam. If this is the case, which is induced by the experiments, there is a measurable loss of iso-α-acids in the hot wort, but at the same time, a gain for the later beer foam retention, as the iso-α-acids will stabilize it. [ABSTRACT FROM AUTHOR]

In this study, the major differences between commercial pale lager beers (PLB) and their non‐alcoholic (NAB) counterparts were characterised by chemical‐analytical and sensory analysis. Chemical‐analytical profiling was performed using standard brewery analyses in addition to gas and liquid chromatography for quantifying volatile and non‐volatile compounds. NAB differed in analytical composition from the PLB, in sugar, aroma, and amino acid profiles. Generally, the PLB contained higher levels of volatile aroma constituents (in particular, significantly higher levels of 2‐methylbutan‐1‐ol, 3‐methylbutan‐1‐ol, ethyl acetate, ethyl hexanoate and ethyl octanoate), specific amino acids (including cysteine, glutamine and alanine), sulphite, glycerol and proteins. NAB show significantly higher concentrations of fermentable sugars (maltose, glucose, fructose and maltotriose), as well as higher levels of amino acids (including threonine, serine and asparagine) and trans‐2‐nonenal. The PLB was similar in analytical composition, whereas the NAB could be discriminated into two clusters, reflecting different sugar profiles, reflecting the production technology. Organoleptic assessment described the flavour of the NAB as 'worty', 'sweet' and 'watery', while the PLB scored higher in 'bitterness intensity' and 'fullness'. Interestingly, those NAB where the analytical profile differed the most from their PLB counterparts exhibited the largest differences in sensory properties. Furthermore, this study suggests synergistic and/or antagonistic effects between groups of chemical compounds which may explain the flavour differences. For instance, high sugar levels suppress the perception of bitterness, whereas sugars, aldehydes and esters impact on the worty flavour of NAB. © 2021 The Institute of Brewing & Distilling [ABSTRACT FROM AUTHOR]

Abstract Aim Neurological disorders are a major public health issue worldwide and are often associated with structural changes in the brain. We have previously demonstrated that iso‐α‐acids (IAAs), the hop‐derived bitter components in beer, improve memory impairment in aged and Alzheimer's disease mouse models. In this study, we evaluated the effects of IAA intake on the brain structure in healthy middle‐aged to older adults. This study was conducted under the Impulsing Paradigm Change through Disruptive Technologies Program (ImPACT) study launched by the Cabinet office of Japan. Method This study employed an open‐labeled, single‐arm, before and after design. Healthy middle‐aged to older adults consumed a beverage containing IAAs (3 mg/190 mL) for 4 weeks.Recently developed magnetic resonance imaging‐based brain health indicators were used to evaluate the following brain conditions: the Brain Healthcare Quotient (BHQ) based on gray matter volume (GM‐BHQ) and white matter fractional anisotropy (FA‐BHQ). Results In total, 25 subjects were recruited, and GM‐BHQ and FA‐BHQ were measured before and after intervention. In all subjects, no significant differences in GM‐BHQ and FA‐BHQ were observed. In subjects aged ≥ 60 years (mean 54.5; standard deviation 3.9) (n = 8), GM‐BHQ was significantly increased 4 weeks after intervention compared with that before intervention. Conclusion Intake of beverages containing IAAs might affect brain aging, particularly in healthy older adults, which may prevent the development of neurological disorders. Future studies employing more robust designs can elucidate the effects of IAAs on GM‐BHQ and cognitive functions.

Beer styles show wide variation in color, flavor, and clarity, due to differences in their chemical content. Some of the major flavor compounds in beer are isomerized alpha acids and phenolic compounds. These were investigated as potentially discerning features between beer styles. A selection of 32 American beers covering five styles was analyzed using liquid chromatography quadrupole time‐of‐flight mass spectrometry, which resulted in high mass accuracy chromatograms of the studied analytes. Distinctions between the presence or relative concentrations of certain compounds were observed and related back to brewing ingredients and procedures. For example, vanillin was only observed in stout beers due to the use of roasted barley malts for brewing, while chlorogenic acid isomers were found in two sours at relatively high concentrations (189 and 34 mg/L) because of the fruits used to flavor the beers. Distinctions were further confirmed using multivariate analysis techniques, which separated three of the five beer styles (India pale ales, stouts, and sours). [ABSTRACT FROM AUTHOR]

Hops are an essential raw material for beer production in the brewery. The hop constituents give the beer its bitter taste, additional aroma, and can make it more stable. As hops are a cost-intensive ingredient, the bitter substance yield plays a major role for breweries. Various approaches are available to increase hop utilization in brewhouses. They range from pre-isomerized hop products or catalysts, which are only utilized outside the German Beer Purity Law, to different procedures, as well as novel brewhouse and dosing equipment. Examples include changes in the mashing process, pre-isomerization systems, or fractional wort boiling. [ABSTRACT FROM AUTHOR]

The changes in hop bitter substances in beer over the course of ageing and the associated decline in sensory quality have been the subject of numerous studies, but none of these have explored if bitter substances react differently during ageing based on whether the hops are added on the hot or on the cold side. To elucidate this a lager beer was brewed with a late aroma hop addition in the brewhouse and additionally dry hopped. Both beers were stored for two years at 4 °C, 22 °C and 30 °C. Overall, ageing the beers at 4 °C resulted in minor changes only. Based on the analysis of the beers aged at 22 °C and 30 °C, the following observations can be drawn: Starting with the cis-iso-α-acids via the bittering units, total iso-α-acids, trans-iso-α-acids and on to the α-acids, the losses of these substances increase significantly. Trans-iso-α-acids are 5 to 8 times more sensitive to degradation than the cis form. The behaviour of co-hulupone was comparatively stable in this regard. A marked difference between the homologs (co-, n- and ad-) of the iso-α-acids could not be found in both beers. However, all of the bitter substances in the dry-hopped beers showed less degradation due to ageing than those in the late-hopped beers. Whether the higher stability of the bitter substances in dry-hopped beer can be attributed to the changes in its composition through the addition of dry hops cannot be clearly established. Additional polyphenols added by dry hopping could potentially provide a “more stable environment” with a higher antioxidative potential. A distinct decrease in xanthohumol was observed; however, it was largely offset by an equivalent increase in isoxanthohumol. Late and dry hopped beers showed no differences with regard to the prenylflavonoids. [ABSTRACT FROM AUTHOR]

In the last decade, with the combined application of high efficiency preparation techniques, high resolution HPLC MS/MS and sophisticated NMR technologies, novel bitter derivatives of α-, iso-α-, β-acids have been identified in beer and model solutions, which has updated our knowledge of hop chemistry. In this review, newly identified cyclic and oxidative products of α-, iso-α-, β-acids in hops and beer, have been comprehensively described to give brewers a more in depth understanding of hop and beer bitterness chemistry. A total of 39 unique substances: 15 derived from α-acids, 15 from iso-α-acids, and 9 derived from β-acids are elucidated, including their structures, suggested formation mechanism, distribution profiles in model solutions or beer, reactions during fermentation, thresholds of some of these compounds, and their evolution during storage. [ABSTRACT FROM AUTHOR]

Dementia and cognitive decline have become worldwide health problems due to rapid growth of the aged population in many countries. We previously demonstrated that single or short-term administration of iso-α-acids, hop-derived bitter acids in beer, improves the spatial memory of scopolamine-induced amnesia model mice in the Y-maze and enhances novel object recognition in normal mice via activation of the vagus nerve and hippocampal dopaminergic system. However, these behavioral tests do not replicate the stimulus conditions or response requirements of human memory tests, and so may have poor translational validity. In this report, we investigated the effects of iso-α-acids on visual discrimination (VD) and reversal discrimination (RD) using a touch panel-based operant system similar to that used for human working memory tests. In the VD task, scopolamine treatment reduced correct response rate and prolonged response latency in mice, deficits reversed by prior oral administration of iso-α-acids. In the RD task, administration of iso-α-acids significantly increased correct response rate compared to vehicle administration. Previous studies have reported that dopamine signaling is involved in both VD and RD learning, suggesting that enhancement of dopamine release contributes to improved memory performance in mice treated with iso-α-acids. Taken together, iso-α-acids improve VD and RD learning, which are considered high-order cognitive functions. Given the translational advantages of the touch panel-based operant system, the present study suggests that iso-α-acids could be effective for improvement of working memory in human dementia patients.

Dementia and cognitive decline are global public health problems. Moderate consumption of alcoholic beverages reduces the risk of dementia and cognitive decline. For instance, resveratrol, a polyphenolic compound found in red wine, has been well studied and reported to prevent dementia and cognitive decline. However, the effects of specific beer constituents on cognitive function have not been investigated in as much detail. In the present review, we discuss the latest reports on the effects and underlying mechanisms of hop-derived bitter acids found in beer. Iso-α-acids (IAAs), the main bitter components of beer, enhance hippocampus-dependent memory and prefrontal cortex-associated cognitive function via dopamine neurotransmission activation. Matured hop bitter acids (MHBAs), oxidized components with β-carbonyl moieties derived from aged hops, also enhance memory functions via norepinephrine neurotransmission-mediated mechanisms. Furthermore, the effects of both IAAs and MHBAs are attenuated by vagotomy, suggesting that these bitter acids enhance cognitive function via vagus nerve stimulation. Moreover, supplementation with IAAs attenuates neuroinflammation and cognitive impairments in various rodent models of neurodegeneration including Alzheimer's disease. Daily supplementation with hop-derived bitter acids (e.g., 35 mg/day of MHBAs) may be a safe and effective strategy to stimulate the vagus nerve and thus enhance cognitive function. [ABSTRACT FROM AUTHOR]

Aim: Neurological disorders are a major public health issue worldwide and are often associated with structural changes in the brain. We have previously demonstrated that iso‐α‐acids (IAAs), the hop‐derived bitter components in beer, improve memory impairment in aged and Alzheimer's disease mouse models. In this study, we evaluated the effects of IAA intake on the brain structure in healthy middle‐aged to older adults. This study was conducted under the Impulsing Paradigm Change through Disruptive Technologies Program (ImPACT) study launched by the Cabinet office of Japan. Method: This study employed an open‐labeled, single‐arm, before and after design. Healthy middle‐aged to older adults consumed a beverage containing IAAs (3 mg/190 mL) for 4 weeks.Recently developed magnetic resonance imaging‐based brain health indicators were used to evaluate the following brain conditions: the Brain Healthcare Quotient (BHQ) based on gray matter volume (GM‐BHQ) and white matter fractional anisotropy (FA‐BHQ). Results: In total, 25 subjects were recruited, and GM‐BHQ and FA‐BHQ were measured before and after intervention. In all subjects, no significant differences in GM‐BHQ and FA‐BHQ were observed. In subjects aged ≥ 60 years (mean 54.5; standard deviation 3.9) (n = 8), GM‐BHQ was significantly increased 4 weeks after intervention compared with that before intervention. Conclusion: Intake of beverages containing IAAs might affect brain aging, particularly in healthy older adults, which may prevent the development of neurological disorders. Future studies employing more robust designs can elucidate the effects of IAAs on GM‐BHQ and cognitive functions. [ABSTRACT FROM AUTHOR]

Beer is an incredibly complex beverage containing more than 3000 different compounds, including carbohydrates, proteins, ions, microbes, organic acids, and polyphenols, among others. Beer becomes even more complex during storage, for over time it may undergo chemical changes that negatively affect the flavor, aroma, and appearance. Thus, it can be expected that maintaining the quality of beer throughout its lifetime is a difficult task. Since it is such a popular drink throughout the world, being familiar with proper analytical techniques for beer evaluation is useful for researchers and brewers. These techniques include, but are not limited to, gas chromatography, liquid chromatography, matrix assisted laser desorption/ionization, capillary electrophoresis, mass spectrometry, ultraviolet–visible spectroscopy, and flame ionization detection. This review aims to summarize the various ingredients and components of beer, discuss how they affect the finished product, and present some of the analytical methods used for quality control and understanding the formation of chemicals in beer during the brewing process. Image 1 • Comprehensive review of beer ingredient and finished product analysis. • Coverage of organic, inorganic, biochemical, and biological constituents. • Avenues for quality control and research in craft beer analysis. [ABSTRACT FROM AUTHOR]

Dementia and cognitive decline have become worldwide health problems due to rapid growth of the aged population in many countries. We previously demonstrated that single or short-term administration of iso-α-acids, hop-derived bitter acids in beer, improves the spatial memory of scopolamine-induced amnesia model mice in the Y-maze and enhances novel object recognition in normal mice via activation of the vagus nerve and hippocampal dopaminergic system. However, these behavioral tests do not replicate the stimulus conditions or response requirements of human memory tests, and so may have poor translational validity. In this report, we investigated the effects of iso-α-acids on visual discrimination (VD) and reversal discrimination (RD) using a touch panel-based operant system similar to that used for human working memory tests. In the VD task, scopolamine treatment reduced correct response rate and prolonged response latency in mice, deficits reversed by prior oral administration of iso-α-acids. In the RD task, administration of iso-α-acids significantly increased correct response rate compared to vehicle administration. Previous studies have reported that dopamine signaling is involved in both VD and RD learning, suggesting that enhancement of dopamine release contributes to improved memory performance in mice treated with iso-α-acids. Taken together, iso-α-acids improve VD and RD learning, which are considered high-order cognitive functions. Given the translational advantages of the touch panel-based operant system, the present study suggests that iso-α-acids could be effective for improvement of working memory in human dementia patients. [ABSTRACT FROM AUTHOR]

The hop isomerization reaction during the brewing process is interfered by many factors such as wort composition and time resulting in significant bitter substance losses. A novel mash filtration system provides new possibilities, as four wort flows (instead of one) are separated in parallel and thus different wort characteristics are available for enhancing the hop isomerization rate. A laboratory-scale screening experiment was performed to investigate the different effects of the wort parameters beyond the conventional brewhouse range. Based on previous industrial field trials, the boundary parameters (minimum and maximum) of the laboratory-scale wort fractions, corresponding to filter modules 1 and 4, were adjusted accordingly to the pH value (pH 5.6 or 7.0) and original gravity (17.0 or 2.0°P). The parameters boiling time and dosing quantity of α-acids were adapted to conventional brewhouse standards as well as to the novel system. Additionally, the influence of magnesium (0.0 or 40.0 mg/L) dosed to the wort on the isomerization reaction was tested. The results showed that the boiling time at a pH value of 5.6 had more influence on the inversion to iso-α-acids than with a wort pH of 7.0. Even with a high original gravity of 17.0°P, an extension of the boiling time showed no significant effect on the isomerization rate. [ABSTRACT FROM AUTHOR]

To investigate the chemical and sensorial impact of dry hopping time on typical pale ale, a standardized beer was produced and separated into ten vessels. Nine vessels were dry hopped, and one vessel remained un-hopped as a control. Impact of dry hopping contact time was investigated over 96 h. Polyphenols and iso-α-acid t/c ratio were analyzed in both Young and Aged beer samples. Total polyphenol content generally increased in both young and aged treatments compared to controls. Analysis of the t/c ratio suggests that both Young and Aged beers were chemically preserved to some degree after approximately 12 h at the given dry hopping rate regardless of age. Within the Aged beer trials, 96 h of dry hop contact yielded a significant increase in t/c ratio compared to all other Aged trials. This suggests that a 4-day dry hop regime may yield additional oxidative protection of iso-α-acids in beers stored unrefrigerated for 30 days. Descriptive analysis was also performed with an 8-person, trained panel; however, beers were sensorially distinguished by their aging time as opposed to their dry hopping time.

For centuries, natural medicines have represented the only option for treating human diseases and, nowadays, plant phytochemicals are considered as promising compounds to treat or prevent chronic conditions. Among them, hop flowers (Humulus lupulus L.), typically used in brewing industries to give the typical aroma and flavor to beer, have attracted particular attention for their health promoting properties. Several in vivo/vitro studies and human interventional trials have demonstrated the beneficial effects of these molecules on weight gain, lipid metabolism, glucose homeostasis, insulin sensitivities, and inflammation by acting on different targets. All these activities suggest a possible role of bitter hop acid in preventing metabolic syndrome and its related diseases. A systematic quest on PubMed and Scopus databases was performed to identify pre-clinical and clinical studies focusing on this topic. This systematic review summarizes the results obtained by different cell lines, animal models, and human interventional trials to propose iso-α-acids as medical nutrition therapy to treat or prevent metabolic syndrome and its related disorders as diabetes, dislipidemia inflammation, etc.

Due to the growth in aging populations worldwide, prevention and therapy for age-related cognitive decline and dementia are in great demand. We previously demonstrated that long-term intake of iso-α-acids, which are hop-derived bitter compounds found in beer, prevent Alzheimer’s pathology in a rodent model. On the other hand, the effects of iso-α-acids on neural activity in Alzheimer’s disease model mice have not been investigated. Here, we demonstrated that short-term intake of iso-α-acids suppresses inflammation in the hippocampus and improves memory impairment even after disease onset. Importantly, we demonstrated that short-term administration of iso-α-acids attenuated the neural hyperactivation in hippocampus. In 6-month-old 5 × FAD mice exhibiting hippocampus inflammation and memory impairment, oral administration of iso-α-acids for 7 days reduced inflammatory cytokines, including MIP-1α and soluble Aβ and improved object memory in the novel object recognition test. In 12-month-old J20 mice, intake of iso-α-acids for 7 days also suppressed inflammatory cytokines and soluble Aβ in the brain. Manganese-enhanced magnetic resonance imaging (MEMRI) of hippocampi of J20 mice showed increased manganese compared with wild type mice, but iso-α-acids canceled this increased MEMRI signal in J20 mice, particularly in the hippocampus CA1 and CA3 region. Taken together, these findings suggest that short-term intake of iso-α-acids can suppress hippocampus inflammation even after disease onset and improve hyper neural activity in Alzheimer’s disease model mice.

With the aging population rapidly increasing worldwide, preventive measures and treatments for age-related cognitive decline and dementia are of utmost importance. We have previously demonstrated that the consumption of iso-α-acids (IAA), which are hop-derived bitter compounds in beer, prevents the formation of disease pathology in a transgenic mouse model of Alzheimer’s disease (AD). However, the effect of IAA consumption on age-related cognitive decline is unknown. In the present study, we examined the effect of long-term and short-term dietary consumption of IAA, on age-related memory impairments and inflammation in the hippocampus of aged mice. When compared with young mice, aged mice showed impairment in spatial working memory during the Y-maze spontaneous alternation test, impairment in object recognition memory during the novel object recognition test (NORT), a pro-inflammatory hippocampal microglial phenotype with increased CD86 expression and inflammatory cytokine production, increased levels of glutamate and amyloid β1–42, and decreased levels of dopamine (DA). In aged mice fed IAA for 3 months, the age-related alterations in memory, microglial inflammation, and glutamate, amyloid β1–42, and DA levels were all significantly attenuated. Additionally, the oral administration of IAA for 7 days in aged mice with memory impairment, also improved spatial and object recognition memory. These results suggest that IAA consumption prevents inflammation in the hippocampus and ameliorates age-related cognitive decline.

Due to the growth in aging populations worldwide, prevention and therapy for age-related cognitive decline and dementia are in great demand. We previously demonstrated that long-term intake of iso-α-acids, which are hop-derived bitter compounds found in beer, prevent Alzheimer's pathology in a rodent model. On the other hand, the effects of iso-α-acids on neural activity in Alzheimer's disease model mice have not been investigated. Here, we demonstrated that short-term intake of iso-α-acids suppresses inflammation in the hippocampus and improves memory impairment even after disease onset. Importantly, we demonstrated that short-term administration of iso-α-acids attenuated the neural hyperactivation in hippocampus. In 6-month-old 5 × FAD mice exhibiting hippocampus inflammation and memory impairment, oral administration of iso-α-acids for 7 days reduced inflammatory cytokines, including MIP-1α and soluble Aβ and improved object memory in the novel object recognition test. In 12-month-old J20 mice, intake of iso-α-acids for 7 days also suppressed inflammatory cytokines and soluble Aβ in the brain. Manganese-enhanced magnetic resonance imaging (MEMRI) of hippocampi of J20 mice showed increased manganese compared with wild type mice, but iso-α-acids canceled this increased MEMRI signal in J20 mice, particularly in the hippocampus CA1 and CA3 region. Taken together, these findings suggest that short-term intake of iso-α-acids can suppress hippocampus inflammation even after disease onset and improve hyper neural activity in Alzheimer's disease model mice. [ABSTRACT FROM AUTHOR]

With the aging population rapidly increasing worldwide, preventive measures and treatments for age-related cognitive decline and dementia are of utmost importance. We have previously demonstrated that the consumption of iso-α-acids (IAA), which are hop-derived bitter compounds in beer, prevents the formation of disease pathology in a transgenic mouse model of Alzheimer's disease (AD). However, the effect of IAA consumption on age-related cognitive decline is unknown. In the present study, we examined the effect of long-term and short-term dietary consumption of IAA, on age-related memory impairments and inflammation in the hippocampus of aged mice. When compared with young mice, aged mice showed impairment in spatial working memory during the Y-maze spontaneous alternation test, impairment in object recognition memory during the novel object recognition test (NORT), a pro-inflammatory hippocampal microglial phenotype with increased CD86 expression and inflammatory cytokine production, increased levels of glutamate and amyloid β1–42, and decreased levels of dopamine (DA). In aged mice fed IAA for 3 months, the age-related alterations in memory, microglial inflammation, and glutamate, amyloid β1–42, and DA levels were all significantly attenuated. Additionally, the oral administration of IAA for 7 days in aged mice with memory impairment, also improved spatial and object recognition memory. These results suggest that IAA consumption prevents inflammation in the hippocampus and ameliorates age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Brewing water is one of the basic raw materials for beer production and knowledge of its composition and pH is essential for the proper conduct of the entire brewing process. In this study, it was observed how the composition of water influences OG values, content of B vitamins, organic acids and iso-α-acids. For brewing, synthetic water was prepared by adding chemicals to deionized water. Models of hard (pH 8.47 ±0.08) and soft (pH 7.68 ±0.23) synthetic water were used for brewing pale bottom-fermented lager beers. Samples of wort, hopped wort, young beer and beer were collected during beer production. HPLC-DAD was used for B vitamins and iso-α-bitter acids quantification. Determination of organic acids was done by ion chromatography with conductivity detector. Obtained data were statistically processed with ANOVA (Analysis of Variance) and interval of confidence was set to 95%. According to the statistical analysis, water composition affects analytes content during beer production and in the final product. Hard water seemed to be a better extraction buffer and its composition (pH) positively affected some processes during brewing technology. One of them was obtaining higher OG values compared to soft water. The beer made from hard water also contained more B vitamins. Composition of brewing water had no influence neither on concentration of organic acids nor on iso-α-acids in conditions of homebrewing. [ABSTRACT FROM AUTHOR]

Abstract Cognitive decline and dementia are currently recognized as major problems in the aging population; however, there is still no promising treatment for these conditions. Previously, our group reported that iso-α-acids (IAAs), which are hop-derived bitter components present in beer, prevent inflammation and cognitive impairment in an Alzheimer's disease model mice (5xFAD mice) and yield significant reduction in amyloid β (Αβ) in the brain. However, data on the molecular mechanisms underlying these physiological effects of IAAs remain limited. Here, we used transcriptome analysis and found that oral administration of IAAs to 5xFAD mice for 7 days induces a 58.9-fold increase in the expression of transthyretin (TTR; Ttr) in the hippocampus compared with controls. In addition, real-time quantitative PCR showed that oral administration of IAAs significantly increased Ttr transcription in the hippocampi of wild type C57BL/6J mice but not in the cerebral cortex. TTR is an Αβ protein scavenger; thus, an increase in its expression could prevent amyloid aggregate formation. These results indicate that IAAs reduce Αβ in the brain by elevating TTR levels. [ABSTRACT FROM AUTHOR]

Historically, hop cones (Humulus lupulus) have been used since ancient times as a remedy for many ailments and, as a source of polyphenols and bitter acids, is very effective in the treatment of metabolic syndrome (MS). Hop flavonoids, particularly xanthohumol (XN), are substances with hypoglycemic, antihyperlipidemic, and antiobesity activities. Iso-α-acids (IAA) and matured hop bitter acids (MHBA) improve health by influencing lipid metabolism, glucose tolerance, and body weight. The modulatory effect of IAA and MHBA on lipid metabolism may also be responsible for a loss in body weight. These results suggest promising applications for IAA, MHBA, and XN in humans, particularly in the prevention of diet-induced obesity and diabetes. [ABSTRACT FROM AUTHOR]

The impact of hop variety and hop aroma on perceived beer bitterness intensity and character was investigated using analytical and sensory methods. Beers made from malt extract were hopped with 3 distinctive hop varieties (Hersbrucker, East Kent Goldings, Zeus) to achieve equi-bitter levels. A trained sensory panel determined the bitterness character profile of each singly-hopped beer using a novel lexicon. Results showed different bitterness character profiles for each beer, with hop aroma also found to change the hop variety-derived bitterness character profiles of the beer. Rank-rating evaluations further showed the significant effect of hop aroma on selected key bitterness character attributes, by increasing perceived harsh and lingering bitterness, astringency, and bitterness intensity via cross-modal flavour interactions. This study advances understanding of the complexity of beer bitterness perception by demonstrating that hop variety selection and hop aroma both impact significantly on the perceived intensity and character of this key sensory attribute. [ABSTRACT FROM AUTHOR]

The chemical analysis of hop-derived humulone and isohumulone components in hops and beer was investigated using multiple injections in a single experimental run (MISER) extracted ion LC-MS. Comparative analysis of the humulone and lupulone contents of 12 hop varieties was accomplished in a 12 min run, an equivalent time of 1 min per hop sample. Rapid analysis of a group of 70 different beers in 74 min provided a comparative assessment of the amount of humulones (α-acids) and the isomerized isohumulones (iso-α-acids) present, also in an equivalent time of 1 min per sample. The relative humulone/isohumulone content was evaluated in a scatter plot, which allowed profiling of various craft and commercial beer styles. The MISER LC-MS approach allows for high-throughput analysis and a significant time savings. Together, these provide opportunities for increasing analysis sampling in production or a simple, rapid chemical analysis to accompany educational or classroom instruction. [ABSTRACT FROM AUTHOR]

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.

An isomerization process of the α-acids contained in hop extract (with magnesium oxide, potassium hydroxide and magnesium peroxide as catalysts at ambient temperature) was carried out. The influence of two factors (the amount of applied catalyst and the isomerization time) was studied. Ultra-high performance liquid chromatography was used for the evaluation of the isomerization process. The best results were obtained with magnesium oxide. In this case, the influence of the operating variables on the isomerization process and optimal process parameters were determined using statistical methods. The isomerization method described above could be carried out with high efficiency without heating and could be easily adopted and applied on an industrial scale. Copyright © 2016 The Institute of Brewing & Distilling [ABSTRACT FROM AUTHOR]

The main bittering component in beer, hop iso-α-acids, have been characterised as weak acids, which act as ionophores impairing microbial cells' function under acidic conditions as present in beer. Besides medium pH, divalent cations play a central role regarding the efficacy of the antimicrobial effect. The iso-α-acids' non-bitter derivatives humulinic acids can be found in isomerised hop extracts and can be generated during hop storage. Therefore, they have been under investigation concerning their influence on beer sensory properties. This study sketches the molecular mechanism behind iso-α-acids' antimicrobial activity in Lactobacillus ( L. ) brevis regarding their ionophore activity versus the dependence of the inhibitory potential on manganese binding, and suggests humulinic acids as novel tasteless food preservatives. We designed and synthesised chemically modified iso-α-acids to enhance the basic understanding of the molecular mechanism of antimicrobial iso-α-acids. It could be observed that a manganese-binding dependent transmembrane redox reaction (oxidative stress) plays a crucial role in inhibition. Privation of an acidic hydroxyl group neither erased ionophore activity, nor did it entirely abolish antimicrobial activity. Humulinic acids proved to be highly inhibitory, even outperforming iso-α-acids. [ABSTRACT FROM AUTHOR]

Due to the harsh environment, microorganisms encounter in beer, spoilage bacteria must be able to customise their metabolism and physiology in an order to master various kinds of perturbations. Proteomic approaches have been used to examine differences between various beer spoilage bacteria and between different stress conditions, such as acid and hop ( Humulus lupulus ) stress. However, these investigations cannot detect changes in low molecular weight (lmw) proteins (<150 amino acids). Therefore, for the first time, we herein present data from a proteomic study of lmw proteins for two Lactobacillus ( L. ) brevis strains exposed to acid stress or, respectively, two different qualities of hop induced stress. We used MALDI-TOF MS as analytical tool for the detection of lmw stress response proteins due to its high sensitivity and low throughput times. Comparing a hop-sensitive and a hop-tolerant strain, detection of the fatty acid biosynthesis-associated acyl carrier protein varied between different stress conditions and incubation times. The findings coincide with previous studies of our group regarding the fatty acid cell membrane composition of beer spoiling L. brevis . It is demonstrated that MALDI-TOF MS is a fast tool to detect and characterise stress situations in beer spoiling bacteria along the lmw sub-proteome. [ABSTRACT FROM AUTHOR]

• MF was carried out at concentration (MF/CO) and diafiltration (MF/DF) operation mode. • MF/DF presented better bitter substances permeation ∼81 % than MF/CO with ∼69 % • NF membranes allowed high bitter substances retention (>90 %) in particularly NF90, XN45, and HL. • NF90 showed severe fouling leading to low permeate fluxes (from ∼34 to 11 L.h−1.m−2) • Proteins and bitter substances were the main fouling agent of MF and NF processes. Crossflow membrane technologies were used to clarify and concentrate the raw extract of bitter substances from hot trub, a brewing by-product, seeking to produce an alternative route for hop products via a study performance and fouling investigation. Microfiltration was performed in concentration (MF/CO) and diafiltration (MF/DF) operation modes, feeding with extract composed of lupulone/analogs (∼6 mg/g), iso -α-acid (∼4 mg/g), and humulones/analogs (∼2 mg/g). The MF/CO had ∼69 % bitter substances permeation, while the MF/DF exhibited an increase of about 22 % in relation to MF/CO only (achieving 81–92 % the bitter substances permeation), being colupulone and n-+adlupulone presenting minor retention (<16 %). Adding the diafiltration step had not modified the profile of permeate fluxes curves, which was close to the exhibited by MF/CO. Concerning the sequential nanofiltration approach, six commercial membranes with different thin-film features and nominal molecular weight cut-offs ranging from 1000 to 150 g/mol (NP010 ≥ UA60 > NP030 > XN45 > NF9 > HL) were tested, operating with a clarified extract from MF/DF. XN45 and HL membranes presented higher bitter substance retention with less flux decay (∼42 %) than others. Membrane surfaces were altered after filtrations in relation to chemical profiles, morphology, and hydrophobicity, indicating a foulant layer formation. Different compositions and morphology of foulant layer were observed, being proteins the principal fouling agent for microfiltration while bitter substances were the main agent for nanofiltrations. [ABSTRACT FROM AUTHOR]

Iso-α-acids (IAAs) can be used as markers for the consumption of beer. Postmortem specimens from a range of coronial cases were analyzed for IAAs in order to determine the prevalence of beer consumption and any correlation to blood alcohol concentrations (BAC). A total of 130 cases were included in this study including those where beer was mentioned in the case circumstances, cases where beer was not mentioned specifically but alcohol was detected, and cases where neither beer was mentioned nor a positive BAC was present. Available blood, serum, vitreous humour and urine specimens were analyzed. Of the 50 cases where beer was mentioned, 86% had one or more IAAs detected. In cases that only had a positive BAC (n = 60), 57% of these cases also showed the presence of these beer markers. IAAs were detected in specimens obtained from traumatized, burnt, and decomposed cases with a mention of beer consumption or where BAC was positive in blood. No IAAs were detected in cases where BAC was negative. There was little or no correlation between blood IAA concentrations and BAC. This study demonstrates the possible detection of IAAs as a marker for beer consumption. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Iso-α-acids (IAA) and reduced IAA can be used as beer-specific ingredient congeners to confirm beer consumption when detected in blood and other specimens using a UHPLC-MS/MS method. Recent analysis of postmortem casework demonstrated a high prevalence of beer consumption and the possibility of providing the source of alcohol in forensic casework. Research outlined in this manuscript has examined the degree to which the interval after death and quality of blood affects the concentration of IAA in postmortem cases. Postmortem whole blood and serum were analyzed in cases where natural or reduced IAA groups were detected. The trans-IAA, cis-IAA, and tetrahydro-IAA (TIAA) groups were subject to postmortem redistribution, although only weakly associated with the length of time from death to collection of specimens. Serum had threefold higher concentrations than blood for trans-IAA, cis-IAA, and TIAA. These studies confirm that although postmortem concentrations cannot be easily compared to concentrations found in living persons the presented findings do provide some understanding to assist in interpretation where the confirmation of beer consumption is required in forensic casework. [ABSTRACT FROM AUTHOR]

BACKGROUND Iso- α-acids and their chemically modified variants are responsible for the bitterness of beer and play a disproportionately large role in the final quality of beer. The current study was undertaken to predict the degradation of commercial lager beers related to changes in the concentration of trans-iso- α-acids during storage by using high-pressure liquid chromatography. RESULTS In the analysed beers the concentration of isohumulone (average concentration 28 mg L−1) was greater than that of isocohumulone (20 mg L−1) and isoadhumulone (10 mg L−1). The kinetic parameters, activation energy and rate constant, of the trans-iso- α-acids were calculated. In the case of dark beers, the activation energy for the degradation of trans-isocohumulones was found to be higher than for trans-isohumulones and trans-isoadhumulones, whereas in pale and alcohol-free beers activation energies for the degradation of the three trans isomers were similar. CONCLUSION The loss of iso- α-acids can be calculated using the activation energy of the degradation of trans-iso- α-acids and the temperature profile of the accelerated ageing. The results obtained in the investigation can be used in the beer industry to predict the alteration of the bitterness of beer during storage. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The long-term stability of the iso-α-acids, and three structurally similar but chemically altered iso-aacids (known as 'reduced iso-α-acids' and consisting of the rho-, tetrahydro- and hexahydro-iso-a-acid groups) were investigated in whole blood. Pools of blank blood spiked with the four beer-specific ingredient congener groups at two different concentration levels were stored at 20 °C, 4 °C and -20 °C; and extracted in duplicate in weeks 1, 3, 5 and 8, using a previously published method. A loss of 15% of the initial concentration was considered to indicate possible instability and losses greater than 30% demonstrated significant losses. The individual analytes within the four iso-α-acid groups were also measured to determine which iso-α-acids were subject to greater degradation and were responsible for the overall group instability. All four iso-α-acid groups showed significant losses after 8 weeks of storage under room temperature conditions in particularly the natural iso-a-acid group where major losses were observed (96% and 85% losses for low and high concentrations, respectively). Some degradation in all iso-α-acid groups were seen at 4 8C samples predominantly due to the 'n' analogs of the groups showing an increased instability in blood. The -20 °C storage conditions resulted in minimal changes in concentrations of all analytes. Higher than frozen storage temperatures can result in substantial changes on the stability of the iso-α-acid type groups in blood. The aim of this study was to highlight the stabilities of the IAA analytes in order to assist in the interpretation of IAA in stored blood specimens. [ABSTRACT FROM AUTHOR]

The use of reduced isomerised hop extracts to achieve both bitterness and light stability became very popular during the last decade. Changes during storage in four hop extracts and seven commercial lager beers are studied using HPLC and spectrophotometric techniques. The degradation of the iso-α-acids and tetrahydro iso-α-acids as a function of time is represented by the ratio, in percentage, of the sum of trans-isomer concentration to the sum of the cis-isomer concentration (T/C). The results provided conclusive evidence that the gradual decreased of bitterness intensity in beer was due to the degradation of iso-α-acids, notably to the instability of the trans-iso-α-acids. When the beers were stored for 14 days at 45°C the decrease of the T/C average varied from 8.6 to 14.0%, except in lemon beer, in which case, T/C decreased 36.9%. The results allowed us to infer that in open storage and/or warm conditions the deterioration of beer was critical above 35°C. On the other hand, the results showed that tetrahydro iso-α-acids remained unaltered. [ABSTRACT FROM PUBLISHER]

Abstract: Many brewing variables, e.g., pH, boiling time, temperature, and the presence of metal catalysts, are essential in view of the isomerisation of hop α-acids into iso-α-acids. In this work, a comparative study on the impact of several selected factors on α-acids isomerisation was performed in both buffer model solutions and wort, in order to find out enhanced boiling conditions for higher isomerisation yields. Increase of the pH of the reaction mixture has a positive effect on the isomerisation yield, in particular in wort, whereas wort gravity only becomes a limiting factor for α-acids conversion at high extract levels. Of the metal catalysts tested, in particular Mg2+, Al3+, and especially Fe3+ showed to have a pronounced positive impact on iso-α-acids formation in wort. However, due to precipitation phenomena, this effect was not observed for Al3+ and Fe3+ in the aqueous buffer model system. Neither the presence of glucose or polyphenols, nor ionic strength seem to exert any influence on α-acids conversion. [Copyright &y& Elsevier]

Abstract: An electronic tongue based on an array of electroactive conducting polymers was developed for the analysis of beers. The principal component analysis (PCA) of the electrochemical signals obtained by immersing the array of electrodes in 21 lager beers (dark and pale; with alcohol and alcohol free) has provided a clear discrimination between dark and pale beers and also between beers with and without alcohol. The correlations between redox processes observed in the electrodes and the iso-α-acids concentration and the alcoholic degree have been found using partial least square regression (PLS2). The Root-Mean-Square Error of Prediction (RMSEP) values for alcoholic strength and iso-α-acids prediction model were 0.603 (%vol) and 9.021 (mgL−1), respectively. [Copyright &y& Elsevier]

Abstract: An electronic tongue (ET) comprising 18 potentiometric chemical sensors was applied to the quantitative analysis of beer. Fifty Belgian and Dutch beers of different types were measured using the ET. The same samples were analyzed using conventional analytical techniques with respect to the main physicochemical parameters. Only non-correlated physicochemical parameters were retained for further analysis, which were real extract, real fermentation degree, alcohol content, pH, bitterness, color, polyphenol and CO2 content. Relationship between the ET and physicochemical datasets was studied using Canonical Correlation Analysis (CCA). Four significant canonical variates were extracted using CCA. Correlation was observed between 6 physicochemical variables (real extract and fermentation degree, bitterness, pH, alcohol and polyphenols’ content) and 14 sensors of the ET. The feasibility of the ET for the quantification of bitterness in beer was evaluated in the aqueous solutions of isomerised hop extract and in the set of 11 beers with bitterness varying between 14 and 38EBU (European Bitterness Units). Sensors displayed good sensitivity to isomerised hop extract and good prediction of the bitterness in beer was obtained. Calibration models with respect to the physicochemical parameters using ET measurements in 50 Belgian and Dutch beer samples were calculated by Partial Least Square regression. The ET was capable of predicting such parameters as real extract, alcohol and polyphenol content and bitterness, the latter with Root Mean Square Error of Prediction (RMSEP) of 2.5. [Copyright &y& Elsevier]

Abstract: Individual iso-α-acids that are responsible for the bitter taste of beer need to be isolated because these acids are required as reference standards in quantitative analysis and when studying the parameters which effect the quality of beer. However, these pure compounds are very expensive, due to inefficient isolation methods. In this study a new isolation method has been developed, in order to reduce the isolation cost. β-Cyclodextrin has been used for the isolation of trans- and cis-iso-α-acids. The separation from the mixture of stereoisomers was achieved by complexation, using ethanol:water (1:2, v/v) as a solvent at a temperature of 50°C for 30min. The molar ratio of iso-α-acids sample to β-cyclodextrin for complexation was 1:1. Precipitation time varied between 9h and 2days, depending on the iso-α-acid. Release of the guest from the cyclodextrin complex was successfully accomplished by elution with methanol. [Copyright &y& Elsevier]

Using pure trans/cis-isocohumulone, trans/cis-isohumulone, and trans/cis-isoadhumulone an isocratic HPLC system has been developed for quantitation of these compounds in hop extracts and beers. The mobile phase contains acetonitrile-water- H 3 PO 4 (50:50:0.01, v/v/v) and is used with a Phenomenex Hypersil 5 µ C 18 column 250×4.6 mm, flow rate 1.5 mL/min. Baseline separation of all 6 isomers was achieved with a total run time of 25 min. The UV spectrum of these pure compounds using this system are quite different. The effect of different mobile phase compositions on separation was investigated as well as the chromatographic parameters, detection limit, and linearity. [ABSTRACT FROM AUTHOR]

A liquid chromatography (LC) method is described for the simultaneous analysis of iso-α-acids and reduced iso-α-acids in beer. Volatile mobile phase additives were selected to enable hyphenation to mass spectrometric (MS) operated in the atmospheric pressure chemical ionization (APCI) mode. Contrary to other recent LC optimization procedures for the same compounds, an alkaline pH was selected hereby improving peak shape and selectivity. Both UV and MS detection are sensitive enough to analyze beers without sample pre-concentration. All major bitter acids are separated within 65 min with exception of cis-dihydroisoadhumulone, which co-elutes with trans-isocohumulone. Due to the selectivity of the MS, these compounds could be differentiated according to their m/z value. The performance in terms of quantification of bitter acids by LC–UV and LC–MS are compared for standard solutions and a selection of 14 beers. [Copyright &y& Elsevier]

Beer has been a popular beverage for thousands of years, and brewers often describe brewing as the oldest biotechnological process. Beer constituents comprise more than 800 compounds and many of them contribute to its flavor characteristics, such as bitterness, sweetness, acidity, hop character, carbonation, alcoholic and fruity or ester flavor, most of which are determined by capillary electrophoresis (CE). CE has recently emerged as a highly promising technique that consumes an extremely small amount of sample and is capable of rapid, high-resolution separation, characterization, and quantitation of analytes. An overview is presented of CE methods currently in use to determine different compounds in beer samples. [Copyright &y& Elsevier]

• This is the first study to elucidate the relationship between IAAs and ICH. • IAAs, a PPAR-g agonist, could improve hematoma resolution and the outcome of ICH rats. • M2 microglial transformation was due to the activation of PPAR-γ-CD 36 axis by IAAs. To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism. The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 μl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated. IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662. This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression. [ABSTRACT FROM AUTHOR]