alpha-bitter-acid and xanthohumol

Beer is one of the earliest human inventions and globally the most consumed alcoholic beverage in terms of volume. In addition to water, the 'German Beer Purity Law', based on the Bavarian Beer Purity Law from 1516, allows only barley, hops, yeasts and water for beer brewing. The extracts of these ingredients, especially the hops, contain an abundance of polyphenols such as kaempferol, quercetin, tyrosol, ferulic acid, xanthohumol/isoxanthohumol/8-prenylnaringenin, α-bitter acids like humulone and β-bitter acids like lupulone. 8-prenylnaringenin is the most potent phytoestrogen known to date. These compounds have been shown to possess various anti-bacterial, anti-inflammatory, anti-oxidative, anti-angiogenic, anti-melanogenic, anti-osteoporotic and anti-carcinogenic effects. Epidemiological studies on the association between beer drinking and skin disease are limited while direct evidence of beer compounds in clinical application is lacking. Potential uses of these substances in dermatology may include treatment of atopic eczema, contact dermatitis, pigmentary disorders, skin infections, skin ageing, skin cancers and photoprotections, which require an optimization of the biostability and topical delivery of these compounds. Further studies are needed to determine the bioavailability of these compounds and their possible beneficial health effects when taken by moderate beer consumption.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Beer; Coumaric Acids; Cyclohexenes; Flavanones; Flavonoids; Humans; Kaempferols; Phenylethyl Alcohol; Phytoestrogens; Propiophenones; Quercetin; Skin; Skin Diseases; Terpenes; Xanthones

Hops contain flavonoids that have sedative and sleep-promoting activities such as α-acid, β-acid, and xanthohumol. In this study, the sleep-enhancing activity of a Saaz-Saphir hops mixture was measured. In the caffeine-induced insomnia model, the administration of a Saaz-Saphir mixture increased the sleep time compared to Saaz or Saphir administration alone, which was attributed to the increase in NREM sleep time by the δ-wave increase. Oral administration of the Saaz-Saphir mixture for 3 weeks increased the γ-amino butyric acid (GABA) content in the brain and increased the expression of the GABA

Topics: Acids; Animals; Bicuculline; Caffeine; Cyclohexenes; Disease Models, Animal; Electroencephalography; Flavonoids; GABA-A Receptor Agonists; gamma-Aminobutyric Acid; Humans; Humulus; Hypnotics and Sedatives; Mice; Picrotoxin; Propiophenones; Receptors, GABA-A; Sleep; Sleep Initiation and Maintenance Disorders; Terpenes

Bacterial biofilms pose a serious medical problem due to their significant resistance to antimicrobials, and staphylococci are recognized as the most frequent cause of biofilm-associated infections. The hop plant (Humulus lupulus L.) contains substances that have been determined to act as anti-infective agents against bacteria, mainly in planktonic form. Therefore, we decided to investigate the antibiofilm properties of H. lupulus L.-derived compounds (humulone, lupulone and xanthohumol) against a selected group of Staphylococcus spp., including methicillin-susceptible and resistant strains. All tested hop compounds were shown to possess antimicrobial properties against all tested staphylococci, both planktonic and biofilm-dwelling, with no significant difference between resistant and susceptible strains. All compounds lowered the number of bacterial cells released from the biofilm, with the strongest effect seen for lupulone, followed by xanthohumol. Moreover, lupulone and xanthohumol were not only able to penetrate the biofilm and reduce the number of bacteria within it, but their higher concentrations (∼60 μg/mL for xanthohumol and ∼125 μg/mL for lupulone) reduced the number of surviving bacterial cells to zero.

Topics: Anti-Bacterial Agents; Biofilms; Cell Line; Cell Survival; Cyclohexenes; Flavonoids; Humans; Humulus; Microbial Sensitivity Tests; Plant Extracts; Propiophenones; Staphylococcus; Terpenes

Anaerobic bacteria, such as Bacteroides fragilis or Clostridium perfringens, are part of indigenous human flora. However, Clostridium difficile represents also an important causative agent of nosocomial infectious antibiotic-associated diarrhoea. Treatment of C. difficile infection is problematic, making it imperative to search for new compounds with antimicrobial properties. Hops (Humulus lupulus L.) contain substances with antibacterial properties. We tested antimicrobial activity of purified hop constituents humulone, lupulone and xanthohumol against anaerobic bacteria. The antimicrobial activity was established against B. fragilis, C. perfringens and C. difficile strains according to standard testing protocols (CLSI, EUCAST), and the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were calculated. All C. difficile strains were toxigenic and clinically relevant, as they were isolated from patients with diarrhoea. Strongest antimicrobial effects were observed with xanthohumol showing MIC and MBC values of 15-107 μg/mL, which are close to those of conventional antibiotics in the strains of bacteria with increased resistance. Slightly higher MIC and MBC values were obtained with lupulone followed by higher values of humulone. Our study, thus, shows a potential of purified hop compounds, especially xanthohumol, as alternatives for treatment of infections caused by select anaerobic bacteria, namely nosocomial diarrhoea caused by resistant strains.

Topics: Anaerobiosis; Anti-Bacterial Agents; Bacteroides fragilis; Clostridioides difficile; Clostridium perfringens; Cross Infection; Cyclohexenes; Diarrhea; Enterocolitis, Pseudomembranous; Flavonoids; Humans; Humulus; Microbial Sensitivity Tests; Plant Extracts; Propiophenones; Symbiosis; Terpenes

Humulus lupulus (hop plant) has long been used in traditional medicine as a sedative and antimicrobial agent. More recently, attention has been devoted to the phytoestrogenic activity of the plant extracts as well as to the anti-inflammatory and chemopreventive properties of the prenylated chalcones present. In this study, an Italian sample of H. lupulus cv. "Cascade" has been investigated and three new compounds [4-hydroxycolupulone (6), humudifucol (7) and cascadone (8)] have been purified and identified by means of NMR spectroscopy along with four known metabolites. Notably, humudifucol (7) is the first prenylated dimeric phlorotannin discovered in nature. Because structurally related phloroglucinols from natural sources were found previously to inhibit microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), the isolated compounds were evaluated for their bioactivity against these pro-inflammatory target proteins. The prenylated chalcone xanthohumol inhibited both enzymes at low μM concentrations.

Topics: Arachidonate 5-Lipoxygenase; Chalcones; Flavonoids; Humulus; Intramolecular Oxidoreductases; Italy; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phytoestrogens; Plant Extracts; Plants, Medicinal; Polyphenols; Prenylation; Propiophenones; Prostaglandin-E Synthases

The effect of the biologically active prenylated chalcone and potential anticancer agent xanthohumol (1) has been investigated on apoptosis of the T98G human malignant glioblastoma cell line. Compound 1 decreased the viability of T98G cells by induction of apoptosis in a time- and concentration-dependent manner. Apoptosis induced by 1 was associated with activation of caspase-3, caspase-9, and PARP cleavage and was mediated by the mitochondrial pathway, as exemplified by mitochondrial depolarization, cytochrome c release, and downregulation of the antiapoptotic Bcl-2 protein. Xanthohumol induced intracellular reactive oxygen species (ROS), an effect that was reduced by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). Intracellular ROS production appeared essential for the activation of the mitochondrial pathway and induction of apoptosis after exposure to 1. Oxidative stress due to treatment with 1 was associated with MAPK activation, as determined by ERK1/2 and p38 phosphorylation. Phosphorylation of ERK1/2 and p38 was attenuated using NAC to inhibit ROS production. After treatment with 1, ROS provided a specific environment that resulted in MAPK-induced cell death, with this effect reduced by the ERK1/2 specific inhibitor PD98059 and partially inhibited by the p38 inhibitor SB203580. These findings suggest that xanthohumol (1) is a potential chemotherapeutic agent for the treatment of glioblastoma multiforme.

Topics: Acetylcysteine; Antineoplastic Agents; Apoptosis; Caspase 3; Caspase 9; Cyclohexenes; Cytochromes c; Dose-Response Relationship, Drug; Flavonoids; Glioblastoma; Humans; Imidazoles; Italy; Mitogen-Activated Protein Kinases; Molecular Structure; Poly(ADP-ribose) Polymerases; Propiophenones; Pyridines; Reactive Oxygen Species; Terpenes

A new quantification method for hop-derived bitter compounds in beer was developed. By means of LC-MS/MS operating in the multiple reaction monitoring mode, a total of 26 hop-derived bitter compounds, namely, the post-, co-, n-, ad-, pre-, and adpre-congeners of iso-alpha-acids, alpha-acids, and beta-acids, as well as the prenylflavonoid isoxanthohumol and the chalcone xanthohumol, could be simultaneously detected for the first time in a single HPLC run in authentic beer samples without any cleanup procedures. To compensate for the effect of coextracted matrix components in LC-MS/MS analysis, the so-called ECHO technique was applied for the first time as a suitable strategy for the quantitative analysis of the hop-derived bitter compounds in fresh and stored beer. On the basis of quantitative data, the remarkable instability of alpha-acids and trans-iso-alpha-acids was confirmed, and it was observed that the degradation of trans-iso-alpha-acids during the storage of beer is not dependent from the nature of the alkanoyl side chain of the congeners. In contrast, an increase of the concentrations of beta-acids and of the prenylflavonoid isoxanthohumol as well as of the chalcone xanthohumol during the storage of beer was observed.

Topics: Beer; Chromatography, High Pressure Liquid; Cyclohexenes; Flavonoids; Food Preservation; Humulus; Magnetic Resonance Spectroscopy; Odorants; Propiophenones; Tandem Mass Spectrometry; Taste; Terpenes

Seven naturally derived components from hop plant (Humulus lupulus L.) extracts were tested for evaluation of biological activities affecting acne vulgaris. Five strains, Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, Kocuria rhizophila and, Staphylococcus pyogenes, were selected as the main acne-causing bacteria. Hop extracts xanthohumol and the lupulones showed strong inhibitory activities against all of the strains. Although hydrogenated derivatives did not show the same level of activity, naturally occurring xanthohumol, humulones, and lupulones all showed moderate to strong anticollagenase inhibitory activities. Antioxidant capacity was also evaluated with seven different methods based on different reactive oxygen species. Xanthohumol showed the highest activity in total oxygen radical absorbance capacity as well as singlet oxygen absorbance capacity.

Topics: Acne Vulgaris; Actinobacteria; Anti-Bacterial Agents; Antioxidants; Bacteria; Biphenyl Compounds; Cyclohexenes; Flavonoids; Humans; Humulus; Matrix Metalloproteinase 1; Matrix Metalloproteinase 8; Matrix Metalloproteinase Inhibitors; Microbial Sensitivity Tests; Phytotherapy; Picrates; Plant Extracts; Propionibacterium acnes; Propiophenones; Staphylococcus; Terpenes

The research reported here deals with co-action of the hop (Humulus lupulus)-derived anti-bacterial compounds, lupulone and xanthohumol, with several antibiotics. Among the antibiotics investigated for their co-action, polymyxin B sulfate, tobramycin and ciprofloxacin had a positive co-action in inhibiting selected test bacteria. The disc/well-diffusion assay and the minimum inhibitory concentration test (MIC) were employed to determine co-action. Both Gram-positive and Gram-negative bacteria were used in the evaluation. There was some co-action against all Gram-positive bacteria tested. Surprisingly, there was some positive co-action even against certain Gram-negative bacteria but not against others. Particularly, there was no co-action against E.coli. An antibacterial cream with lupulone, neomycin and polymyxin B sulfate was prepared and showed co-action. Ideas for other practical applications of this effect are put forth. The mechanism of the synergistic effect is briefly discussed but no attempt was made to prove it experimentally.

Topics: Anti-Infective Agents; Bacteria; Ciprofloxacin; Cyclohexenes; Drug Combinations; Drug Synergism; Flavonoids; Humulus; Microbial Sensitivity Tests; Plant Extracts; Polymyxin B; Propiophenones; Terpenes; Tobramycin

The concentrations of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol were monitored in the hop varieties Admiral (A), Wye Challenger (WC), and First Gold (FG) during the harvest seasons of 2003 through 2005. Hops grown under an organic regimen were compared to plants grown conventionally in hop fields in close vicinity. The concentrations of the key compounds depended very much on climatological conditions showing, in general, highest levels in poorest weather conditions (2004). Of the three varieties studied, FG was the only one showing a clear trend for higher concentrations of secondary metabolites under organic growing conditions than under conventional farming conditions. Cultivation of A and WC seems to be very sensitive to climatic conditions and environmental stresses caused by pests and diseases, thereby leading to various results. WC proved to be a rich source of bioactive chalcones, particularly desmethylxanthohumol.

Topics: Agriculture; Climate; Cyclohexenes; Flavonoids; Food, Organic; Humulus; Propiophenones; Terpenes

Important secondary metabolites, present in hops (Humulus lupulus L.), include alpha-acids and beta-acids, which are essential for the brewing of beer, as well as the prenylated chalcones, desmethylxanthohumol, and xanthohumol, which exhibit interesting bioactive properties. Their formation and accumulation in five selected hop varieties, Wye Challenger, Wye Target, Golding, Admiral, and Whitbread Golding Variety, were quantitatively monitored by high-performance liquid chromatography using UV detection. All target compounds were present from the onset of flowering, not only in female hop cones but also in male inflorescences, albeit in low concentrations. During development from female inflorescences to cones, levels of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol gradually increased, while each hop variety exhibited individual accumulation rates. Furthermore, these compounds were present in leaves of fully grown hops as well. The study demonstrated that key compounds for flavor and potential beneficial health effects associated with beer not only reside in the glandular lupulin structures but also are distributed over various parts of the hop plant.

Topics: Beer; Chromatography, High Pressure Liquid; Cyclohexenes; Flavonoids; Humulus; Plant Extracts; Propiophenones; Terpenes

We searched hop extract for active component(s) that inhibited bone resorption in the pit formation assay, and isolated xanthohumol and humulone as active ingredients. Especially humulone had extraordinarily strong inhibitory activity and the IC50 (concentration of 50% inhibition) value was 5.9 x 10(-9)M.

Topics: Bone Resorption; Cyclohexenes; Dose-Response Relationship, Drug; Flavonoids; Plant Extracts; Plants, Edible; Propiophenones; Structure-Activity Relationship; Terpenes