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.

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.

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.

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.

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.

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.

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.

Extraction of hops pelletized (Humulus lupulus) with subcritical CO2 and hydrodistillation: Chemical composition identification, kinetic model, and evaluation of antioxidant and antimicrobial activity.

Hop essential oil and hop extract using carbon dioxide (CO2) are products with high added value because they have bioactive and sensory properties. In this context, the objective of this study was to obtain and characterize essential oil and extracts from pelleted hops of El Dorado, Polaris, Hallertau Blanc and Callista varieties using hydrodistillation and subcritical CO2 extraction methods. Extraction yield ranged from 0.38 % to 1.97 % (m/m) for essential oils and from 8.76 % to 15.35 % (m/m) for extracts using subcritical CO2. The chemical compositions of the essential oils were mainly monoterpene (18.14 % to 29.91 %) and sesquiterpene (46.01 % to 59.03 %) hydrocarbons and for the extracts were sesquiterpene hydrocarbons (33.05 % to 71.90 %) and oxygenated sesquiterpenes (14.80 % to 34.89 %). The extracts showed better antioxidant activity than essential oils due to the presence of phenolic compounds and flavonoids. Hop extracts showed some antimicrobial activity, but essential oils did not demonstrate antimicrobial potential. Hop extracts obtained with subCO2 have the potential to be used in the brewing industry as a flavoring and as natural antioxidants.

Preparation of green colorimetric pH sensor using Humulus lupulus L. (common hop) biomolecular extract for sweat monitoring.

Novel smart cotton diagnostic assay was developed toward onsite sensing of sweat pH variations for possible medical applications such as drug test and healthcare purposes. Humulus lupulus L. extract was obtained according to previously reported procedure. As reported by high-performance liquid chromatography (HPLC), the extract demonstrated the presence of hop acids, prenylchalcones, and prenylflavanones, which is responsible for the colorimetric changes. The extract was applied to cellulose fibers employing potassium aluminum sulfate as mordant. This was observed by the formation of mordant/xanthohumol nanoparticles onto cotton surface. The absorption spectra and CIE (Commission Internationale de l'Eclairage) Lab screening of the prepared cotton assay showed colorimetric changes in association with hypsochromic shift from 600 nm to 433 nm upon exposure to sweat simulant fluid (pH < 7). The biochromic activity of the xanthohumol-finished cotton depends mainly on the halochromic performance of the xanthohumol chromophore to show a colorimetric switch from yellow to white owing to intramolecular charge transfer in the xanthohumol molecule. No substantial defects were detected in gas-permeability and stiffness of the treated fabrics. Satisfactory fastness was approved for the xanthohumol-dyed diagnostic cotton assay.

Variability in the levels of fungicide residues in final beer as they are influenced by various sequences of agrochemicals used for treatment on hops.

The fate of during brewing of pesticides (organic compounds and copper) from hops was determined to reveal linkages between various pesticide sequences applied in hop yards and the level of pesticides in beer. For this purpose, laboratory-scale brewing trials were carried out with conventional hops from four localities in which pest control spray programs varied. Pesticide residue analysis in samples of hopped wort, young beer, and beer was carried out by liquid chromatography in tandem with mass spectrometry (LC-MS/MS). Cu concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). The transfer rates (%) of individual pesticides were calculated to demonstrate their ability to be transferred from hops to the brewed solutions. The pesticides exhibited different transfer rates correlating well with their log p values; however, the obtained transfer data were not related to their concentration in hops. The average transfer rates calculated for ametoctradin (15% ± 5%), mandipropamid (38% ± 4%), boscalid (48% ± 5%), and azoxystrobin (47% ± 2%) increased in good correlation with their descending log P values. On the contrary, the transfer rates of copper residues were related to residual concentrations of copper in hops and exhibited logarithmic dependency. The carryover of the sum of all pesticides in the four samples ranged from 36% to 49%, averaging 42% ± 6%. The data showed no substantial influence of various pesticide spray sequences on the percentages of overall pesticide residues carried over into beer.

Chemical compositions and sleep-promoting activities of hop (Humulus lupulus L.) varieties.

Among natural products with sleep-promoting activity, hops have been used since ancient times as a tranquilizer and hypnotic agent. This study investigated the sleep-promoting effects of extracts of various hop (Humulus lupulus L.) varieties in invertebrate and vertebrate models. The content of α-acids, ß-acids, and xanthohumol was higher in hop 70% alcohol extracts than in hop hot water extracts. Among the alcohol extracts, Citra contained a high α-acid content (229.32 µg/mg), while Saphir showed high ß-acid and xanthohumol content (66.37 and 4.23 µg/mg, respectively). In Drosophila melanogaster, Simcoe and Mosaic water extracts and Saphir and Simcoe alcohol extracts significantly increased total nighttime sleep. Total sleep time of mice with pentobarbital-induced sleep was significantly increased by Simcoe and Mosaic water extracts and Saphir and Simcoe ethanol extracts compared to the normal group. Oral administration of Simcoe water extract and Saphir alcohol extract improved sleep in the caffeine-induced insomnia model and upregulated the mRNA expression of GABAA (gamma 2 subunit) and GABAB receptors in mouse brains. Additionally, Saphir alcohol extract significantly increased the GABA content in mouse brains. Simcoe water extract and Saphir ethanol extract modulated GABAergic signaling to improve sleep-related behaviors, including sleep duration.

Hop Latent Viroid: A Hidden Threat to the Cannabis Industry.

Hop latent viroid (HLVd) is the biggest concern for cannabis and hop growers worldwide. Although most HLVd-infected plants remain asymptomatic, research on hops has demonstrated a decrease in both the α-bitter acid and terpene content of hop cones, which affects their economic value. The HLVd-associated "dudding" or "duds" disease of cannabis was first reported in 2019 in California. Since then, the disease has become widespread in cannabis-growing facilities across North America. Although severe yield loss associated with duds disease has been recorded, little scientific information is available to growers in order to contain HLVd. Consequently, this review aims to summarise all of the scientific information available on HLVd so as to be able to understand the effect of HLVd on yield loss, cannabinoid content, terpene profile, disease management and inform crop protection strategies.

Humulus lupulus L. Extract Protects against Senior Osteoporosis through Inhibiting Amyloid ß Deposition and Oxidative Stress in APP/PS1 Mutated Transgenic Mice and Osteoblasts

As aging progresses, ß-amyloid (Aß) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). Humulus lupulus L. (hops) is an important medicinal plant widely used in the food, beverage and pharmaceutical industries due to its strong antioxidant ability. In this study, APP/PS1 mutated transgenic mice and Aß-injured osteoblasts were used to evaluate the protective effects of hops extracts (HLE) on SOP. Mice learning and memory levels were assessed by the Morris water maze. Mice femurs were prepared for bone micro-structures and immunohistochemistry experiments. The deposition of Aß in the hippocampus, cortex and femurs were determined by Congo red staining. Moreover, protein expressions related to antioxidant pathways were evaluated by Western blotting. It was found that HLE markedly improved learning abilities and ameliorated memory impairment of APP/PS1 mice, as well as regulated antioxidant enzymes and bone metabolism proteins in mice serum. Micro-CT tests indicated that HLE enhanced BMD and improved micro-architectural parameters of mice femur. More importantly, it was discovered that HLE significantly reduced Aß deposition both in the brain and femur. Further in vitro results showed HLE increased the bone mineralization nodule and reduced the ROS level of Aß-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that Humulus lupulus L. extract could protect against senior osteoporosis through inhibiting Aß deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP.

Beyond brewing: ß-acid rich hop extract in the development of a multifunctional polylactic acid-based food packaging.

Hops' (Humulus lupulus L.) phytochemicals are well known for their bioactivity. In the present study, the functional properties of hop extract rich in ß-acids, as potassium-salts structures (KBA), were investigated to develop a sustainable active food packaging. Polylactic acid (PLA)-based sheets were incorporated with increasing concentrations of hop extract (0.1-5 % w/w in terms of KBA) and characterized through performance and bioactive properties. KBA-added sheets presented decreased crystallinity and affected mechanical and thermal properties, especially with higher KBA amounts. The sheets' surface hydrophobicity gradually decreased by KBA-extract addition, while the water vapor permeability was not affected. A Fickian diffuse behavior and a better fit to application in fatty foods were observed during release tests. UV-blocking and antioxidant properties were improved by KBA incorporation. Furthermore, results from antibacterial assays revealed great susceptibility of Staphylococcus aureus and Listeria monocytogenes towards sheets added with 5 % of KBA. Moreover, the atomic force microscopy (AFM) observations revealed that KBA led to strong effects on the cell membranes of both bacteria, including disruption of membrane integrity and cell death. Therefore, this study is a sign of great prospects of hop ß-acids use, as KBA compound, in the production of sustainable active packaging for safe food shelf-life extension.

Compound of Cynanchum wilfordii and Humulus lupulus L. Ameliorates Menopausal Symptoms in Ovariectomized Mice.

Cynanchum wilfordii and Humulus lupulus L. have been used for their various pharmacological properties in South Korea as a traditional medicine or health functional food, respectively, and their intake may relieve menopausal symptoms. The purpose of current study was to determine the effect of compound of Cynanchum wilfordii and Humulus lupulus L. (CWHL) in menopausal symptoms of ovariectomized (OVX) mice. OVX mice received CWHL or caudatin (an active ingredient of CWHL) once daily for 7 weeks. Values for hypothalamic serotonin (5-HT), dopamine, norepinephrine, estrogen receptor (ER)-ß, 5-HT1A, and 5-HT2A were significantly enhanced, while value for hypothalamic monoamine oxidase A was reduced in CWHL and caudatin groups compared with the OVX group. CWHL and caudatin significantly reduced tail skin temperature and rectal temperature of OVX mice through partial recovering of the levels of serum estrogen, nitric oxide, follicle-stimulating hormone, luteinizing hormone, and receptor-activator of the NF-κB ligand (RANKL). Moreover, CWHL and caudatin improved bone mineral density via decreasing levels of serum RANKL, tartrate-resistant acid phosphatase, and collagen type 1 cross-linked N-telopeptide and improving levels of serum alkaline phosphatase, osteoprotegerin, and osteocalcin compared with the OVX group without adverse effects such as dyslipidemia. CWHL increased uterine ER-ß levels but did not change uterus and vaginal weights. Taken together, the results indicate that CWHL may relieve menopausal symptoms by controlling depression-, hot flashes-, and osteoporosis-associated biomarkers. Therefore, we propose that CWHL might be a safe and potential candidate for management of menopause as a health functional food.