colupulone and cohumulone

Topics: Antioxidants; Cyclohexanones; Drug Design; Free Radical Scavengers; Humans; Linoleic Acid; Lipoproteins, LDL; Oxidation-Reduction; Phloroglucinol; Prenylation

Bitter acids (BAs) from the hop plant Humulus lupulus L. exhibit multiple beneficial biological properties with promising effects in cancer therapy and prevention, but information regarding the effects on hepatocellular carcinoma (HCC) is missing. Here, we used two different hop bitter acid extracts enriched for either α-acids or β-acids to obtain insight into whether biological activity varies between these two groups of BAs. At a concentration of 25 µg/ml, only the β-acid rich started to induce aspartate transaminase (AST) release, and a significant increase was detected with 50 µg/ml of both extracts. Already at lower concentrations both extracts led to a dose-dependent inhibition of proliferation, and migration was suppressed at a concentration as low as 5 µg/ml in HCC cells. The focus on different signaling pathways revealed an inhibition of ERK1/2 phosphorylation, downregulation of AP-1 activity and an alleviation of nuclear factor κB (NFκB) activity in HepG2 cells incubated with 5 µg/ml of both extracts, whereby the β-acid rich extract showed more pronounced effects. In conclusion, we identified ERK1/2, AP-1 and NFκB, which are important factors in tumor development and progression, as targets of hop BAs. Thus, these data suggest the potential use of BAs as functional nutrients for both prevention and treatment of HCC.

Topics: Acids; Antineoplastic Agents, Phytogenic; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Cell Movement; Cell Proliferation; Cyclohexanones; Cyclohexenes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Humulus; Liver Neoplasms; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Phosphorylation; Plant Extracts; Terpenes; Transcription Factor AP-1; Tumor Cells, Cultured

A method of high performance liquid chromatography (HPLC) was developed for the separation and determination of six acidic components (cohumulone, humulone, adhumulone, colupulone, lupulone and adlupulone) in hops extracts. The effects of several important factors, such as the addition of acid, the organic solvent of elution solution and the column temperature, were investigated to acquire the optimum conditions. The separation was carried out on a Hypersil ODS2 column (250 mm x 4. 6 mm, 5 microm). A mixture of acetonitrile-0. 1% (v/v) phosphoric acid solution (pH 2. 2) (65: 35, v/v) was used as the mobile phase at a flow rate of 1. 0 mL/min in isocratic elution mode. The column temperature was kept at room temperature, and the detection wavelength was set at 315 nm. The six acidic components reached baseline separation, and were identified by ultraviolet spectroscopy, infrared spectroscopy and mass spectrometry. The results show that this method is suitable for the analysis of acidic components in hops extracts owing to the stable and simple performance.

Topics: Acids; Chromatography, High Pressure Liquid; Cyclohexanones; Cyclohexenes; Humulus; Plant Extracts; Terpenes

Wild hops (Humulus lupulus L.) are potential new germplasms to expand the variability of genetic resources for hop breeding. We evaluated Canadian (62 plants) and Caucasian (58 plants) wild hops by their chemical characteristics and with molecular genetic analyses using sequence-tagged site and simple sequence repeat markers, in comparison with European (104 plants) and North American (27 plants) wild hops. The contents of alpha and beta acids varied from 0.36% to 5.11% and from 0.43% to 6.66% in Canadian wild hops, and from 0.85% to 3.65% and from 1.22% to 4.81% in Caucasian wild hops, respectively. The contents of cohumulone and colupulone distinctly differed between European and North American wild hops: the cohumulone level in alpha acids was in the range 46.1%-68.4% among North American wild hops and in the range 13.6%-30.6% among European wild hops. The high content of myrcene and the low contents of humulene, farnesene, and selinenes were typical for wild hops from Canada, in contrast to wild hops from the Caucasus region. We compared the chemical characteristics with molecular genetic data. Chemical characteristics differentiated wild hops into North American and Eurasian groups. Molecular genetic analysis was able to separate Caucasian wild hops from European wild hops. We proved a hop phylogeny by means of wide molecular analysis.

Topics: Canada; Cyclohexanones; Cytochrome P-450 Enzyme System; Humulus; Minisatellite Repeats; Phylogeny; Polymorphism, Genetic; Russia; Sequence Tagged Sites