Hop (Humulus lupulus L.) extract reverts glycaemic imbalance and cognitive impairment in an animal model of obesity.

The rates of overweight and obesity around the world have increased in past years. The body's adipose tissue stimulates the antioxidant and oxidation imbalance capacity at the cellular level. This scenario favors an inflammatory low-grade systemic condition starting with insulin resistance, which in turn may involve diabetes mellitus type 2 and cognitive decline afterward. Neurological diseases have been correlated to senile age diseases over time. This scenario calls for a change in the incidence of obesity in the younger generation. An unhealthy dietary consumption together with sedentary habits might lead to poor gut absorption of nutrients. Several plants and foods have bioactive compounds that can reduce or inhibit radical scavengers, reactive oxygen species, and metal ion complexes that threaten the cerebral defense system. The bitter acids from hops (Humulus lupulus L.) have been demonstrated to have promising effects on lipid and carbohydrate metabolism improvement, reducing inflammatory responses through alpha acids, beta acids, and analogs action. Therefore, the current study aimed to investigate the bioactivity of hop bitter acids in obese and lean mice. For that, a dry hop extract (DHE) was obtained by applying carbon dioxide as the fluid of supercritical extraction. Afterward, seventy-eight male mice of the C57BL/6J strain were weighed and randomly distributed into six groups of 13 animals each according to the diet offered: (NO) normolipidic diet, (NO1) normolipidic diet containing 0.35% alpha acids, (NO2) normolipidic diet containing 3.5% alpha acids, (HP) hyperlipidic diet, (HP1) hyperlipidic diet containing 0.35% alpha acids, and (HP2) hyperlipidic diet containing 3.5% alpha acids. After applying the glycemic tolerance and insulin tolerance tests, a better stabilization of glycemia levels and weight gain among those animals fed with DHE (NO2 and HP2) were observed in comparison to the obese control group (HP) (p < 0.05). There was also an amelioration of antioxidant capacity observed by checking the enzymatic profile by SOD and an apparent mitigation of brain degeneration by checking GSK3ß and p-IRS1 proteins expression (p < 0.05). The y-maze cognitive test applied to highlight possible obesity-harmful animal brains did not indicate a statistical difference between the groups. Although the weekly dietary intake between the obese HP2 group (33.32 ± 4.11, p < 0.05) and control HP (42.3 ± 5.88, p < 0.05) was different. The bioactive compounds present in DHE have demonstrated relevant effects on glycemic control, insulin signaling, and the consequent modulatory action of the obesity-related markers with the brain's inflammatory progression.

Effect of Xanthohumol, a Bioactive Natural Compound from Hops, on Adenosine Pathway in Rat C6 Glioma and Human SH-SY5Y Neuroblastoma Cell Lines.

Xanthohumol (Xn) is an antioxidant flavonoid mainly extracted from hops (Humulus lupulus), one of the main ingredients of beer. As with other bioactive compounds, their therapeutic potential against different diseases has been tested, one of which is Alzheimer's disease (AD). Adenosine is a neuromodulatory nucleoside that acts through four different G protein-coupled receptors: A1 and A3, which inhibit the adenylyl cyclases (AC) pathway, and A2A and A2B, which stimulate this activity, causing either a decrease or an increase, respectively, in the release of excitatory neurotransmitters such as glutamate. This adenosinergic pathway, which is altered in AD, could be involved in the excitotoxicity process. Therefore, the aim of this work is to describe the effect of Xn on the adenosinergic pathway using cell lines. For this purpose, two different cellular models, rat glioma C6 and human neuroblastoma SH-SY5Y, were exposed to a non-cytotoxic 10 µM Xn concentration. Adenosine A1 and A2A, receptor levels, and activities related to the adenosine pathway, such as adenylate cyclase, protein kinase A, and 5'-nucleotidase, were analyzed. The adenosine A1 receptor was significantly increased after Xn exposure, while no changes in A2A receptor membrane levels or AC activity were reported. Regarding 5'-nucleotidases, modulation of their activity by Xn was noted since CD73, the extracellular membrane attached to 5'-nucleotidase, was significantly decreased in the C6 cell line. In conclusion, here we describe a novel pathway in which the bioactive flavonoid Xn could have potentially beneficial effects on AD as it increases membrane A1 receptors while modulating enzymes related to the adenosine pathway in cell cultures.

The effects of a brand-specific, hemp-derived cannabidiol product on physiological, biochemical, and psychometric outcomes in healthy adults: a double-blind, randomized clinical trial.

BACKGROUND: Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid derived from the Cannabis sativa plant. CBD exhibits various interactions at receptor sites, prompting the research of its potential anti-inflammatory, immunomodulatory, psychological, and pain-relieving effects. This study aimed to investigate the physiological, biochemical, and psychometric effects of a brand-specific, hemp-derived CBD product in healthy adults over a 12-week observation period. METHODS: 54 healthy males and females (age = 25 ± 7y; BMI = 24.82 ± 3.25 kg/m2) recruited from a large Southeastern University completed the study. Participants arrived at the laboratory after > 8 h of fasting, and > 48 h without alcohol consumption and vigorous exercise. Following baseline measurements (height, weight, blood pressure, electrocardiogram (ECG), and blood work), participants were stratified by sex and randomized to either CBD or placebo groups. Products were administered double-blinded, with both given in liquid form containing medium-chain triglyceride oil, while the CBD product specifically contained 50 mg/mL of CBD. Participants were instructed to consume 1 mL of their product twice daily and were given enough product to last until their next laboratory visit. Data were collected at baseline and on days 30 ± 3, 60 ± 3, and 90 ± 3. Blood was drawn for analysis of immune and inflammatory biomarkers. Chronic pain among participants was calculated using urine samples according to the foundational pain index (FPI). Self-reported psychometric questionnaires were utilized (Cohen's Perceived Stress Scale, Pittsburgh Sleep Quality Index, Profile of Mood States,10-item Likert scale for perceived pain) to assess stress, sleep quality, mood state, and body discomfort. To determine overall wellbeing, participants completed a daily survey indicating if they missed work or school due to illness. Change from baseline was calculated for each measure, and mixed effects models were used to determine differences between groups over time while adjusting for baseline values (α = 0.05). Data are presented as mean ± standard deviation. RESULTS: There were no Group-by-Time interactions or Group or Time main effects for immune or inflammatory biomarkers (p > 0.05). Analyses revealed no Group-by-Time interactions or main effects observed for perceived stress, sleep quality, overall mood disturbance, and all the profile of mood state subscales (p > 0.05), except "vigor-activity." A Time main effect was found for the sub-score for "vigor-activity" (p = 0.007; Pre CBD = 19.5 ± 5.2, Post CBD = 17.3 ± 5.3; Pre PL = 19.0 ± 5.7, Post PL = 17.9 ± 7.1), which decreased from Visit 3 to Visit 4 (p = 0.025) and from Visit 3 to Visit 5 (p = 0.014). There was a Group main effect for FPI (p = 0.028; Pre CBD = 11.9 ± 14.4, Post CBD = 8.8 ± 10.9; Pre PL = 9.0 ± 14.2, Post PL = 12.9 ± 11.5), indicating that the placebo group had greater increases in pain over the intervention compared to the CBD group. No significant differences were found between groups in the incidence and prevalence of "colds or flus" (p > 0.05). DISCUSSION: CBD was safe and well tolerated in healthy adults. These findings show pain was lower in the CBD group, suggesting a potentially positive effect for consumption of CBD. "Vigor-activity" decreased across the intervention, which may be a confounding effect of the academic semester. While the dosage chosen was safe, more research may be warranted using higher doses as these may be needed to observe further therapeutic effects in healthy populations.

Comparison of α and ß-acid isomerization in hops and beer using HPLC, confocal microscopy, spectrofluorimetry and chemical analysis of metabolites and essential oils in flowers of different hop cultivars produced in Brazil.

We used confocal microscopy and spectrofluorescence to characterize the emission spectra in hop flowers, to follow the isomerization processes in different hop preparations, and beers, to compare with HPLC extracted samples. Flowers of different hop cultivars produced in three regions of Brazil, were quantitated by HPLC and GC-MS. The fluorescence spectra showed two characteristic emission bands evaluated from different preparations. The isomerization process leads to a gradual decrease in fluorescence intensity as the reaction progresses. This demonstrates the valuable use of confocal microscopy and fluorescence spectroscopy for analysis of the correlation between bitter acid indices with fluorescence intensity and lifetime microscopy. Such techniques can be used directly in the flowers allowing rapid monitoring of the brewing process. Twenty-nine substances were characterized in the essential oils and some cultivars presented quantities of bitter acids and essential oil levels close to those expected for plants after more than three years of cultivation.

Comparison of polyfunctional thiol, element, and total essential oil contents in 32 hop varieties from different countries.

Volatile thiol 3-mercaptohexan-1-ol (3MH) and particularly 4-mercapto-4-methylpentan-2-one (4MMP) are highly potent flavour compounds in hops. For the determination, a simple and robust stable isotope dilution LC-MS/MS method was developed and applied to 32 hop varieties worldwide from harvest years 2019 and 2020. Limit of detection, precision, and recovery were 0.15 µg/kg, 10%, and 97-108%, respectively. Levels of 3MH and 4MMP ranged from 1.9 to 79.2 µg/kg and from undetectable to 37.1 µg/kg, respectively. Citra, Mosaic, and Strata were rich in both thiols. ICP analyses revealed, that variation of potassium content between the two harvest years was inversely correlated with that of manganese and rubidium (|r| ≥ 0.89) among 12 US varieties excluding Citra and Mosaic. Total essential oil content (0.34-2.7 mL/100 g) was inversely correlated with calcium content (|r| ≥ 0.65). Greatly varying thiol levels depending on variety, region and harvest year might lead to differing flavour results in beer.

Optimization of Antifungal Properties of Hop Cone Carbon Dioxide Extracts Based on Response Surface Methodology.

Response surface methodology (RSM) was employed to optimize the process parameters of the supercritical carbon dioxide extraction of hop cones in terms of their antifungal properties against Fusarium culmorum and Aspergillus niger. The effects of temperature (40-50 °C), pressure (200-300 bar), and CO2 consumption (25-75 kgCO2/kg) on the extraction yield, content of α- and ß-acids, as well as pathogens' growth inhibition were investigated. Both pressure and CO2 consumption had a significant effect on antifungal properties. It was observed that the best results for antifungal properties were obtained when hop cones were extracted with pure carbon dioxide at the temperature of 50 °C, under the pressure of 300 bar with CO2 consumption at the level of 75 kgCO2/kg of feed for extraction. The highest antifungal properties of hop cone supercritical carbon dioxide extracts were analyzed as 100% for Fusarium culmorum and 68% for Aspergillus niger, calculated as the growth inhibition of tested pathogens. The aim of the study was to determine the optimum values of extraction parameters to achieve the maximum response and enable us to investigate the interaction of these parameters on the antifungal properties of hop cone extracts.

Protective Effect of Hop Ethyl Acetate Extract on Corticosterone-Induced PC12 and Improvement of Depression-like Behavior in Mice.

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.

α acid fraction from Hop extract exerts an endothelium-derived hyperpolarization vasorelaxant effect through TRPV4 employing the feedforward mechanism of PKCα.

Until now, the beneficial vascular properties of Hop reported in the literature have been mainly attributed to specific compound classes, such as tannins and phenolic acids. However, the potential vascular action of a Hop subfraction containing a high amount of α or ß acids remains completely understood. Therefore, this study aims to investigate the vascular effects of the entire Hop extract and to fraction the Hop extract to identify the main bioactive vascular compounds. A pressure myograph was used to perform vascular reactivity studies on mouse resistance arteries. Phytocomplex fractionation was performed on a semi-prep HPLC system and characterized by UHPLC-PDA-MS/MS coupled to mass spectrometry. Western blot analysis was performed to characterize the phosphorylation site enrolled. The entire Hop extract exerts a direct dose-dependent endothelial vascular action. The B1 subfraction, containing a high concentration of α acids, recapitulates the vascular effect of the crude extract. Its vasorelaxant action is mediated by the opening of Transient Receptor Potential Vanilloid type 4 (TRPV4), potentiated by PKCα, and subsequent involvement of endothelial small-conductance calcium-activated potassium channels (SKCa) and intermediate-conductance calcium-activated potassium channels (IKCa) that drives endothelium-dependent hyperpolarization (EDH) through heterocellular myoendothelial gap junctions (MEGJs). This is the first comprehensive investigation of the vascular function of Hop-derived α acids in resistance arteries. Overall, our data suggest that the B1 subfraction from Hop extracts, containing only α acids, has great potential to be translated into the useful armamentarium of natural bioactive compounds with cardiovascular benefits.

Exploring the composition and potential uses of four hops varieties through different extraction techniques.

Hydrophilic, lipophilic extracts and essential oil of four hops varieties from Slovenia were examined in this study. Lipophilic extracts were obtained by supercritical extraction (SFE), while for hydrophilic extracts ultrasound and microwave extraction were employed. Essential oils were isolated by the hydrodistillation process. The lipophilic composition of essential oils and lipophilic extracts was determined by GC-MS analysis. Monoterpenes and sesquiterpene hydrocarbons were the most abundant class of compounds in oils (62.27-79.65 %), with myrcene being the most abundant constituent. Limonene and trans-caryophyllene were two terpenes determined in all essential oils while only trans-caryophyllene was detected in SFE samples. Antioxidant, antimicrobial, and cytotoxic activity, determined by applying in vitro assays, was more influenced by extraction technique than by varieties. Molecular docking was carried out to gain insight into the potential cancer protein targets BCL-2 and MMP9, whereby humulene epoxide II displayed good binding configuration within the cavities of the two proteins.

Xanthohumol-A Miracle Molecule with Biological Activities: A Review of Biodegradable Polymeric Carriers and Naturally Derived Compounds for Its Delivery.

Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review.

Humulus lupulus aqueous extract and hydrolate as a potential ingredient for cosmetics: chemical characterization and in vitro antimicrobial, cytotoxicity, antioxidant and anti-inflammatory assessment.

Humulus lupulus extracts have in their composition different molecules, such as polyphenols, α-acids, ß-acids, and hydrocarbons, which contribute to the plant's medicinal properties. These molecules are associated with antimicrobial, antioxidant and anti-inflammatory activities. OBJECTIVE: This work focuses on the evaluation of H. lupulus biological activities, with the aim of evaluating its potential for inclusion in cosmetic formulations. METHODS: Two distinct aqueous extracts and two hydrolates obtained via hydrodistillation were evaluated. These include the flower parts (FE, FH) and the mix of aboveground parts (ME, MH). The chemical profiles for both aqueous extracts and hydrolates were identified by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Antimicrobial, antioxidant, cytotoxicity, and anti-inflammatory activity were tested in vitro using standard methods. RESULTS: Rutin was the major compound found in FE (40.041 µg mg-1 of extract) and ME (2.909 µg mg-1 of extract), while humulenol II was the most abundant compound in hydrolates (FH: 20.83%; MH: 46.80%). Furthermore, FE was able to inhibit the growth of Staphylococcus aureus and Staphylococcus epidermis with MIC values of 50% and 25% (v/v), respectively. FH showed the same effect in Staphylococcus aureus (50% v/v). FH evidenced poor antioxidant potential in DPPH scavenging test and demonstrated significant antioxidant and anti-inflammatory effects by reducing (***p < 0.001) intracellular reactive oxygen species (ROS), NO (nitric oxide) levels (***p < 0.001) and cyclooxygenase-2 (COX-2) protein expression (***p < 0.001) in lipopolysaccharide (LPS)-stimulated macrophages. Nevertheless, it is important to note that FH exhibited cytotoxicity at high concentrations in 3T3 fibroblasts and RAW 264.7 macrophages. CONCLUSION: The studied H. lupulus aqueous extracts and hydrolates revealed that FH stands out as the most promising bioactive source for cosmetic formulations. However, future research addressing antimicrobial activity is necessary to confirm its potential incorporation into dermatological and cosmetic formulations.

Unlocking hot trub's potential: a simple method for extracting bitter acids and xanthohumol.

BACKGROUND: Hot trub is a macronutrient- and micronutrient-rich by-product generated in the brewing industry, which is still underrated as a raw material for reprocessing purposes. In this context, this study aimed to investigate the extraction of bitter acids' and xanthohumol from hot trub as well as identify the significance of parameters for the process. The research assessed various extraction parameters, such as pH, ethanol concentration, temperature, and solid-to-liquid ratio, using a Plackett-Burman design. RESULTS: Ethanol concentration and pH were the most significant parameters affecting extraction yield. ß-acids were found to be the principal components of the bitter acids, with a maximum concentration near 16 mg g-1, followed by iso-α-acids and α-acids achieving 6 and 3.6 mg g-1, respectively. The highest yields of bitter acids were observed in the highest ethanol concentration, while pH was relevant to extraction process in treatments with low ethanol ratios. Concerning the xanthohumol extraction, the approach achieved maximum concentration (239 µg g-1) in treatments with ethanol concentration above 30%. Despite their variances, the phytochemicals exhibited comparable extraction patterns, indicating similar interactions with macromolecules. Moreover, the characterization of the solid residues demonstrated that the extraction process did not bring about any alterations to the chemical and total protein profiles. CONCLUSION: Ethanol concentration was found to have the most significant impact on the extraction of bitter acids and xanthohumol, while temperature had no significant effect. The solid remains resulting from the extraction showed potential for use as a protein source. © 2024 Society of Chemical Industry.

Quantification of Hop-Derived Bitter Compounds in Beer Using Liquid Chromatography Mass Spectrometry.

Hops (Humulus lupulus L.) are essential raw materials for beer brewing, and the major contributors to beer bitterness are isohumulones (iso-α-acids) and humulinones. In recent years, many breweries have focused on the production of hop-forward beer styles by adding hops after or during the cold fermentation stage, which will tend to release humulinones or other hop-derived bitter compounds. In this study, a LC-MS/MS method was developed for quantification of 60 hop-derived bitter compounds in 25 min. Reverse-phase chromatography with an alkaline methanol/acetonitrile (70:30) mobile phase was used for the separation. The quantitative range was 0.053-3912 ng/mL with correlation coefficient r > 0.99, and the LOQ were 0.26 and 0.053 ng/mL for iso-α-acids and humulinones. Precision (RSD < 5.0%) and accuracy (recovery 86.3%-118.1%) were both satisfactory. The abundance of hop-derived bitter compounds in the dry-hopped beer (Double-India Pale Ale) and the nondry-hopped beer (Vienna Lager) were monitored throughout the fermentation and storage stages, and the formation of oxidation and cyclization products showed difference profiles between these two beers. The quantification results reveal how hop-derived bitter compounds change throughout the brewing process, as well as the influence of hops and brewing techniques on beer bitterness.

Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L.) exerts multidirectional pro-healing properties towards damaged zebrafish hair cells by regulating the innate immune response.

Xanthohumol (XN) is a prominent prenylated flavonoid present in the hop plant (Humulus lupulus L.). Despite undoubted pro-healing properties of hop plant, there is still a need for clinical investigations confirming these effects as well as the underlying molecular mechanisms. The present study was designed to (1) establish the role of XN in non-invasive inflammation induced by chemical damage to zebrafish hair cells, (2) clarify if it influences cell injury severity, neutrophil migration, macrophage activation, cell regeneration, and (3) find out whether it modulates the gene expression profile of chosen immune and stress response markers. All experiments were performed on 3 dpf zebrafish larvae. After fertilization the embryos were transferred to appropriate XN solutions (0.1 µM, 0.3 µM and 0.5 µM). The 40 min 10 µM CuSO4 exposure evoked severe damage to posterior lateral line hair cells triggering a robust acute inflammatory response. Four readouts were selected as the indicators of XN role in the process of inflammation: 1) hair cell death, 2) neutrophil migration towards damaged hair cells, 3) macrophage activation and recruitment to damaged hair cells, 4) hair cell regeneration. The assessments involved in vivo confocal microscopy imaging and qPCR based molecular analysis. It was demonstrated that XN (1) influences death pathway of damaged hair cells by redirecting their severe necrotic phenotype into apoptotic one, (2) impacts the immune response via regulating neutrophil migration, macrophage recruitment and activation (3) modulates gene expression of immune system markers and (4) accelerates hair cell regeneration.

Compounds derived from Humulus lupulus inhibit SARS-CoV-2 papain-like protease and virus replication.

BACKGROUND: Selected natural compounds exhibit very good antiviral properties. Especially, the medicinal plant Humulus lupulus (hop) contains several secondary plant metabolites some of which have previously shown antiviral activities. Among them, the prenylated chalcone xanthohumol (XN) demonstrated to be a potent inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). HYPOTHESIS/PURPOSE: Following the finding that xanthohumol (XN) is a potent inhibitor of SARS-CoV-2 Mpro, the effect of XN and its major derivatives isoxanthohumol (IXN), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN) from hops on SARS-CoV-2 papain-like protease (PLpro) were investigated. STUDY DESIGN: The modulatory effect of the hop compounds on PLpro were studied first in silico and then in vitro. In addition, the actual effect of hop compounds on the replication of SARS-CoV-2 in host cells was investigated. METHODS: In silico docking analysis was used to predict the binding affinity of hop compounds to the active site of PLpro. A recombinant PLpro was cloned, purified, characterized, and analyzed by small-angle X-ray scattering (SAXS), deISGylation assays, and kinetic analyses. Antiviral activity of hop compounds was assessed using the fluorescently labeled wildtype SARS-CoV-2 (icSARS-CoV-2-mNG) in Caco-2 host cells. RESULTS: Our in silico docking suggests that the purified hop compounds bind to the active site of SARS-CoV-2 PLpro blocking the access of its natural substrates. The hop-derived compounds inhibit SARS-CoV-2 PLpro with half maximal inhibitory concentration (IC50) values in the range of 59-162 µM. Furthermore, we demonstrate that XN and 6-PN, in particular, impede viral replication with IC50 values of 3.3 µM and 7.3 µM, respectively. CONCLUSION: In addition to the already known inhibition of Mpro by XN, our results show, for the first time, that hop-derived compounds target also SARS-CoV-2 PLpro which is a promising therapeutic target as it contributes to both viral replication and modulation of the immune system. These findings support the possibility to develop new hop-derived antiviral drugs targeting human coronaviruses.

Structure and genetic diversity of Canadian Maritimes wild hops.

Studies on the northeastern American native hops (Humulus lupulus ssp. lupuloides) from the Canadian Maritimes are scarce. This study aimed to evaluate the genetic structure and diversity among 25 wild-collected hops from three Canadian Maritime provinces using microsatellite (simple sequence repeat (SSR)) markers. Based on 43 SSR markers, four distinct subgroups were found, with a low molecular variance (19%) between subgroups and a high variance (81%) within subgroups. The Nei's unbiased genetic distance between clusters ranged from 0.01 to 0.08, the genetic distance between clusters 2 and 3 being the farthest and that between clusters 1 and 2 the closest. Cluster 2 captured the highest overall diversity. A total of 18 SSR markers clearly discriminated hop clones by detecting putative subspecies-specific haplotypes, differentiating clones of native-wild H. lupulus ssp. lupuloides from the naturalized old and modern hop cultivars. Seven of the 18 SSR markers also differentiated two clones from the same site from one another. The study is the first, using molecular markers, to identify SSR markers with potential for intellectual property protection in Canadian Maritimes hops. The SSR markers herein used can be prime tools for hop breeders and growers in the region.

Insight into the aroma quality of 'Callista' cultivar of hop (Humulus lupulus L.): Impact of harvest timing, year, and location.

Hops (Humulus lupulus L.) are essential ingredients in brewing, contributing to beer's flavor, aroma, and stability. This study pioneers an in-depth analysis of the 'Callista' cultivar, aiming to unravel how harvest timing, annual variations, and cultivation location synergistically influence its molecular profile, sensory perception, and biochemistry. Leveraging high-performance liquid chromatography and gas chromatography-mass spectrometry-olfactometry, we identified significant year-to-year and location-based fluctuations in bitter acids-the quintessential aroma constituents in hops. Our comprehensive aroma profiling discerned 55 volatile compounds, marking the first-ever sensory detection of 2-butanone in hops, with its presence showing remarkable interannual variability. This study showed significant differences among the three years tested, whereas hops were perceived "fruitier" and more "citrusy" in 2021, even though the bitter acid and aroma analysis showed that 2022 sticks out due to extremely high lupulone values up to 10% dry cone weight and 78% ß-myrcene in the oil fraction compared to 60% and 45% in 2020 and 2021, respectively. Molecular analysis of key enzymes involved in hop aroma biosynthesis revealed no significant associations with location, but a strong diurnal pattern for all genes. The results indicated that especially the hot temperatures of 2022 may have induced significant changes of cone quality, while 2021 was more interesting from the sensory evaluations, which may justify the usage of viticultural terms such as "vintage" for hop marketing. These findings contribute to a better understanding of the factors influencing hop aroma and quality.

Aroma Profile Development in Beer Fermented with Azacca, Idaho-7, and Sultana Hops.

Hops are among the most costly and environmentally impactful raw materials used in brewing, yet they play a crucial role in the aroma of beer. However, predicting beer aroma based on hop variety or hopping method remains arduous. This is partly because hop oils are unique for each hop variety, and they may be biotransformed by yeast enzymes during fermentation. Even slight molecular structure modifications can dramatically affect the organoleptic properties of beer. Through combined chemical and sensory analysis of dry-hopped beers prepared with different hop varieties (Azacca, Idaho-7, and Sultana), this work aimed to profile the aromas and the overall biotransformation processes taking place during fermentation. A total of 51 volatile organic compounds (VOCs) were semi-quantified and monitored: 19 esters, 13 sesquiterpenes, 7 ketones, 7 alcohols, 4 monoterpenes, and 1 volatile acid. There were significant similarities in the measured analytes and perceived aromas of these beers, but one hop variety (Sultana) delivered an increased quantity of unique aromas and an increased concentration of volatiles in the headspace for the same quantity of hop pellets added. This work provides practical information to brewers who utilize hops in beer production.

Environmental and agronomic factors that impact the regional identity of Cascade and Mosaic® hops grown in the Pacific Northwest.

BACKGROUND: Regional identity is a well-established concept of economic interest that has been identified as a source of unique quality traits of various agricultural products originating from a specific region. In the context of hops, the exploration of regional identity is still at a very early stage despite an increasing global demand for specialized aroma hops to enable more product diversity, especially in the growing craft beer industry. Thus, we conducted a large-scale investigation characterizing the growing environments of Cascade and Mosaic® hops at 39 field locations throughout two important valleys in the Pacific Northwest region of the United States to identify factors that significantly impact hop characteristics and to better understand how these impact hop regional identity. RESULTS: The Willamette Valley (Oregon) and the Yakima Valley (Washington) have distinctly different soil characteristics, soil chemistry, and climate. In turn, growers in these two regions apply unique agronomic practices in response to these differences. This investigation also revealed significant subregional differences in growing environment within each of these two valleys. Multivariate statistics, correlation, and regression analysis identified a number of environmental and agronomic factors like soil pH, the concentration of zinc, sulfur, and manganese in the soil, and the amount of applied zinc fertilization, which exhibited strong positive or negative correlations with specific hop quality traits depending on the hop variety, primarily in Oregon. CONCLUSION: This study provides new insights into understanding hop regional identity and represents an important step towards fully utilizing this effect. © 2023 Society of Chemical Industry.

Semi-Synthesis of Different Pyranoflavonoid Backbones and the Neurogenic Potential.

Flavonoids and chalcones are known for their manifold biological activities, of which many affect the central nervous system. Pyranochalcones were recently shown to have a great neurogenic potential, which is partly due to a specific structural motif-the pyran ring. Accordingly, we questioned if other flavonoid backbones with a pyran ring as structural moiety would also show neurogenic potential. Different semi-synthetic approaches starting with the prenylated chalcone xanthohumol, isolated from hops, led to pyranoflavanoids with different backbones. We identified the chalcone backbone as the most active backbone with pyran ring using a reporter gene assay based on the promoter activity of doublecortin, an early neuronal marker. Pyranochalcones therefore appear to be promising compounds for further development as a treatment strategy for neurodegenerative diseases.