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Humulus lupulus L., a very popular beer ingredient and medicinal plant: overview of its phytochemistry, its bioactivity, and its biotechnology

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Abstract

Humulus lupulus L. (Cannabaceae), commonly named hop, is widely grown around the world for its use in the brewing industry. Its female inflorescences (hops) are particularly prized by brewers because they produce some secondary metabolites that confer bitterness, aromas and antiseptic properties to the beer. These sought-after metabolites include terpenes and sesquiterpenes, found in essential oil, but also prenylated phenolic compounds, mainly acylphloroglucinols (bitter acids) from the series of α-acids (humulone derivatives). These metabolites have shown numerous biological activities, including among others, antimicrobial, sedative and estrogenic properties. This review provides an inventory of hop’s chemistry, with an emphasis on the secondary metabolites and their biological activities. These compounds of biological interest are essentially produced in female inflorescences, while other parts of the plant only synthetize low quantities of them. Lastly, our article provides an overview of the research in plant biotechnology that could bring alternatives for hops metabolites production.

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References

  • Aberl A, Coelhan M (2012) Determination of volatile compounds in different hop varieties by Headspace-Trap GC/MS—in comparison with conventional hop essential oil analysis. J Agric Food Chem 60(11):2785–2792

    Article  CAS  PubMed  Google Scholar 

  • Abourashed EA, Koetter U, Brattstrom A (2004) In vitro binding experiments with a valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine 11(7–8):633–638

    Article  CAS  Google Scholar 

  • Akazawa H, Kohno H, Tokuda H et al (2012) Anti-inflammatory and anti-tumor-promoting effects of 5-deprenyllupulonol C and other compounds from hop (Humulus lupulus L.). Chem Biodiv 9(6):1045–1054

    Article  CAS  Google Scholar 

  • Akdemir EG (2015) Empirical prediction and validation of antibacterial inhibitory effects of various plant essential oils on common pathogenic bacteria. Int J Food Microbiol 202:35–41

    Article  CAS  Google Scholar 

  • Allsopp P, Possemiers S, Campbell D et al (2013) A comparison of the anticancer properties of isoxanthohumol and 8-prenylnaringenin using in vitro models of colon cancer. BioFactors 39(4):441–447

    Article  CAS  PubMed  Google Scholar 

  • Almaguer C, Schönberger C, Gastl M et al (2014) Humulus lupulus-a story that begs to be told: a review. J Inst Brew 120(4):289–314

    CAS  Google Scholar 

  • Aoshima H, Takeda K, Okita Y et al (2006) Effects of beer and hop on ionotropic gamma-aminobutyric acid receptors. J Agric Food Chem 54(7):2514–2519

    Article  CAS  Google Scholar 

  • Banthorpe DV, Brown JT, Morris GS (1989) Production of trans-β-farnesene by callus of Humulus lupulus. Phytochemistry 28:1847–1849

    Article  CAS  Google Scholar 

  • Bartmanska A, Tronima T, Poplonski J et al (2013) Biotransformations of prenylated hop flavonoids for drug discovery and production. Curr Drug Metab 14(10):1083–1097

    Article  CAS  PubMed  Google Scholar 

  • Batista D, Ascensao L, Sousa MJ et al (2000) Adventitious shoot mass production of hop (Humulus lupulus L.) var. Eroica in liquid medium from organogenic nodule cultures. Plant Sci 151:47–57

    Article  CAS  Google Scholar 

  • Batista PA, Werner MFF, Oliveira EC et al (2008a) Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (−)-linalool in mice. Neurosci Lett 440(3):299–303

    Article  CAS  PubMed  Google Scholar 

  • Batista D, Fonseca S, Serrazina S et al (2008b) Efficient and stable transformation of hop (Humulus lupulus L.) var. Eroica by particle bombardment. Plant Cell Rep 27:1185–1196

    Article  CAS  PubMed  Google Scholar 

  • Behre KE (1999) The history of beer additives in Europe—a review. Veget Hist Archaeobot 8:35–48

    Article  Google Scholar 

  • Bernotienė G, Nivinskenė O, Butkienė R et al (2004) Chemical composition of essential oils of hops growing wild in Aukstaitija (Humulus lupulus L.). Chemija 15(2):31–36

    Google Scholar 

  • Bhattacharya S, Virani S, Zavro M et al (2003) Inhibition of Streptococcus mutans and other oral streptococci by hop (Humulus lupulus L.) constituents. Econ Bot 57(1):118–125

    Article  Google Scholar 

  • Bland JS, Minich D, Lerman R et al (2015) Isohumulones from hops (Humulus lupulus) and their potential role in medical nutrition therapy. PharmaNutrition 3:46–52

    Article  CAS  Google Scholar 

  • Bocquet L, Sahpaz S, Rivière C (2018a) An overview of the antimicrobial properties of hop. In: Mérillon JM, Rivière C (eds) Natural antimicrobial agents, series sustainable development and biodiversity. Springer, New York, pp 31–54

    Chapter  Google Scholar 

  • Bocquet L, Rivière C, Dermont C, Samaillie J, Hilbert JL, Halama P, Siah A, Sahpaz S (2018b) Antifungal activity of hop extracts and compounds against the wheat pathogen Zymoseptoria tritici. Ind Crops Prod 122:290–297

    Article  CAS  Google Scholar 

  • Bohr G, Gerhäuser C, Knauft J et al (2005) Anti-inflammatory acylphloroglucinol derivatives from hops (Humulus lupulus). J Nat Prod 68(10):1545–1548

    Article  CAS  PubMed  Google Scholar 

  • Bolca S, Possemiers S, Maervoet V et al (2007) Microbial and dietary factors associated with the 8-prenylnaringenin producer phenotype: a dietary intervention trial with fifty healthy post-menopausal caucasian women. Br J Nutr 98(5):950–959

    Article  CAS  PubMed  Google Scholar 

  • Bowe J, Li XF, Kinsey-Jones J et al (2006) The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. J Endocrinol 191(2):399–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruneton J (2016) Pharmacognosie, Phytochimie, Plantes médicinales, 5th edn. Lavoisier, Tec & Doc, Paris

    Google Scholar 

  • Buckwold VE, Wilson RJH, Nalca A, Beer BB et al (2004) Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res 61(1):57–62

    Article  CAS  PubMed  Google Scholar 

  • Caballerro I, Blanco CA, Porras M (2012) Iso-alpha-acids, bitterness and loss of beer quality during storage. Trends Food Sci Technol 26:21–30

    Article  CAS  Google Scholar 

  • Calvo-Castro LA, Burkard M, Sus N et al (2018) The oral bioavailability of 8-prenylnaringenin from Hops (Humulus lupulus L.) in healthy women and men is significantly higher than that of its positional isomer 6-prenylnaringenin in a randomized crossover trial. Mol Nutr Food Res 62:1700838

    Article  CAS  Google Scholar 

  • Cattoor K, Bracke M, Deforce D et al (2010) Transport of hop bitter acids across intestinal Caco-2 cell monolayers. J Agric Food Chem 58(7):4132–4140

    Article  CAS  PubMed  Google Scholar 

  • Cattoor K, Remon JP, Boussery K et al (2011) Bioavailability of hop-derived iso-alpha-acids and reduced derivatives. Food Funct 2(7):412–422

    Article  CAS  PubMed  Google Scholar 

  • Cattoor K, Dresel M, De Bock L et al (2013) Metabolism of hop-derived bitter acids. J Agric Food Chem 61(33):7916–7924

    Article  CAS  PubMed  Google Scholar 

  • Čermák P, Palečková V, Houška M et al (2015) Inhibitory effects of fresh hops on Helicobacter pylori strains. Czech J Food Sci 33(4):302–307

    Article  Google Scholar 

  • Čermák P, Olsovska J, Mikyska A et al (2017) Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria. APMIS 125(11):1033–1038

    Article  PubMed  CAS  Google Scholar 

  • Česlová L, Holčapek M, Fidler M et al (2009) Characterization of prenylflavonoids and hop bitter acids in various classes of Czech beers and hop extracts using high-performance liquid chromatography-mass spectrometry. J Chrom A 1216(43):7249–7257

    Article  CAS  Google Scholar 

  • Chadwick LR, Nikolic D, Burdette JE et al (2004) Estrogens and congeners from spent hops (Humulus lupulus). J Nat Prod 67(12):2024–2032

    Article  CAS  PubMed  Google Scholar 

  • Chadwick LR, Pauli GF, Farnsworth NR (2006) The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties. Phytomedicine 13(1–2):119–131

    Article  CAS  PubMed  Google Scholar 

  • Chandra A, Langezaal CR, Scheffer JJC (1991) p-hydroxynonanone in cell suspension cultures of a Humulus lupulus cultivar. Phytochemistry 30:495–496

    Article  CAS  Google Scholar 

  • Chapman AC (1903) Essential oil of hops. J Chem Soc Trans 83:505–513

    Article  CAS  Google Scholar 

  • Chappel CI, Smith SY, Chagnon M (1998) Subchronic toxicity study of tetrahydroisohumulone and hexahydroisohumulone in the beagle dog. Food Chem Toxicol 36(11):915–922

    Article  CAS  PubMed  Google Scholar 

  • Chen QH, Fu ML, Chen MM et al (2012) Preparative isolation and purification of xanthohumol from hops (Humulus lupulus L.) by high-speed counter-current chromatography. Food Chem 132(1):619–623

    Article  CAS  PubMed  Google Scholar 

  • Clark SM, Vaitheeswaran V, Ambrose SJ et al (2013) Transcriptome analysis of bitter acid biosynthesis and precursor pathways in hop (Humulus lupulus). BMC Plant Biol 13:12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collin S (2002) Hop aroma extraction and analysis. In: Jackson JF, Linskens HF (eds) Analysis of taste and aroma. Molecular methods of plant analysis, vol 21. Springer, Berlin, Heidelberg, pp 69–88

    Google Scholar 

  • Collin S, Jerkovic V, Bröhan M et al (2013) Polyphenols and beer quality. In: Ramawat KG, Mérillon JM (eds) Natural products. Springer, Berlin, Heidelberg, pp 2333–2359

    Chapter  Google Scholar 

  • Costa R, Rodrigues I, Guardao L et al (2017) Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice. J Nutr Biochem 45:39–47

    Article  CAS  Google Scholar 

  • De Keukeleire J, Ooms G, Heyerick A et al (2003) Formation and accumulation of α-acids, β-acids, desmethylxanthohumol, and xanthohumol during flowering of hops (Humulus lupulus L.). J Agric Food Chem 51(15):4436–4441

    Article  PubMed  CAS  Google Scholar 

  • De Keukeleire J, Janssens I, Heyerick A et al (2007) Relevance of organic farming and effect of climatological conditions on the formation of α-acids, β-acids, desmethylxanthohumol, and xanthohumol in hop (Humulus lupulus L.). J Agric Food Chem 55(1):61–66

    Article  PubMed  CAS  Google Scholar 

  • Delmulle L, Bellahcene A, Dhooge W et al (2006) Anti-proliferative properties of prenylated flavonoids from hops (Humulus lupulus L.) in human prostate cancer cell lines. Phytomedicine 13:732–734

    Article  CAS  PubMed  Google Scholar 

  • Dhooghe L, Naessens T, Heyerick A et al (2010) Quantification of xanthohumol, isoxanthohumol, 8-prenylnaringenin, and 6-prenylnaringenin in hop extracts and derived capsules using secondary standards. Talanta 83(2):448–456

    Article  CAS  PubMed  Google Scholar 

  • Diller RA, Riepl HM, Rose O et al (2009) Desmethylxanthohumol from hops, chemistry and biological effects. In: Preedy VR (ed) Beer in health and disease prevention. Elsevier, Burlington, San Diego, London, pp 703–709

    Chapter  Google Scholar 

  • Dimpfel W, Suter A (2008) Sleep improving effects of a single dose administration of a valerian/hops fluid extract. Eur J Med Res 13(5):200–204

    PubMed  Google Scholar 

  • Dorn C, Weiss TS, Heilmann J et al (2010a) Xanthohumol, a prenylated chalcone derived from hops, inhibits proliferation, migration, and interleukin-8 expression of hepatocellular carcinoma cells. Int J Oncol 36(2):435–441

    CAS  PubMed  Google Scholar 

  • Dorn C, Bataille F, Gaebele E et al (2010b) Xanthohumol feeding deas not impair organ function and homeostasis in mice. Food Chem Toxicol 48(7):1890–1897

    Article  CAS  PubMed  Google Scholar 

  • Dresel M, Van Opstaele F, Praet T et al (2013) Investigation of the impact of the hop variety and the hop** technology on the analytical volatile profile of single-hopped worts and beers. Brew Sci 66:162

    Google Scholar 

  • Dusek M, Olsovska J, Krofta K et al (2014) Qualitative determination of beta-acids and their transformation products in beer and hop using HR/AM-LC-MS/MS. J Agric Food Chem 62(31):7690–7697

    Article  CAS  PubMed  Google Scholar 

  • Elisabetsky E, Brum LFS, Souza DO (1999) Anticonvulsant properties of linalool in glutamate-related seizure models. Phytomedicine 6(2):107–113

    Article  CAS  PubMed  Google Scholar 

  • Engelson M, Solberg M, Karmas E (1980) Anti-mycotic properties of hop extract in reduced water activity media. J Food Sci 45(5):1175–1178

    Article  CAS  Google Scholar 

  • Etteldorf N, Etteldorf N, Becker H (1999) New chalcones from hop, Humulus lupulus L. Z Naturforsch C 54:610–612

    Article  CAS  Google Scholar 

  • European Medicines Agency (2014) Community herbal monograph on Humulus lupulus L., flos. EMA/HMPC/682384/2013

  • Faivre C, Ghedira K, Goetz P et al (2007) Humulus lupulus L. Phytothérapie 5(2):86–89

    Article  CAS  Google Scholar 

  • Falcone Ferreyra ML, Rius SP, Casati P (2012) Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front Plant Sci 3:222

    CAS  PubMed  PubMed Central  Google Scholar 

  • Farag MA, Porzel A, Schmidt J et al (2011) Metabolite profiling and fingerprinting of commercial cultivars of Humulus lupulus L. (hop): a comparison of MS and NMR methods in metabolomics. Metabolomics 8(3):492–507

    Article  CAS  Google Scholar 

  • Farago J, Psenakova I, Farago N (2009) The use of biotechnology in hop (Humulus lupulus L.) improvement. Nova Biotechnol 9:279–293

    Google Scholar 

  • Farago J, Kluciarovsky F, Psenakova I (2011) Bioactive polyphenols and flavonoids in cell cultures of hops (Humulus lupulus L.). Curr Opin Biotechnol 22S:S15–S152

    Google Scholar 

  • Farber SM, Masten JM, Anderson HH et al (1950) Tolerance and effects of lupulon in man. Dis Chest 18(1):10–15

    Article  CAS  PubMed  Google Scholar 

  • Fernández-García C, Rancan L, Paredes SD et al (2018) Xanthohumol exerts protective effects in liver alterations associated with aging. Eur J Nutr. https://doi.org/10.1007/s00394-018-1657-6

    Article  PubMed  Google Scholar 

  • Forino M, Pace S, Chianese G et al (2016) Humudifucol and bioactive prenylated polyphenols from hops (Humulus lupulus cv. “Cascade”). J Nat Prod 79(3):590–597

    Article  CAS  PubMed  Google Scholar 

  • Fortes AM, Santos F, Pais MS (2010) Organogenic nodule formation in hop: a tool to study morphogenesis in plants with biotechnological and medicinal applications. J Biomed Biotechnol article ID 583691:1–16

    Article  CAS  Google Scholar 

  • Franco L, Sanchez C, Bravo R et al (2012) The sedative effect of non-alcoholic beer in healthy female nurses. PLoS ONE 7(7):e37290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frölich S, Schubert C, Bienzle U et al (2005) In Vitro Antiplasmodial activity of prenylated chalcone derivatives of hops (Humulus lupulus) and their interaction with Haemin. J Antimicrob Chemother 55(6):883–887

    Article  PubMed  CAS  Google Scholar 

  • Frölich S, Schubert C, Jenett-Siems K (2009) Antimalarials from prenylated chalcone derivatives of hops. In: Preedy VR (ed) Beer in health and disease prevention. Academic, San Diego, p 747752

    Google Scholar 

  • Fuchs C, Spiteller G (1996) Rapid and easy identification of isomers of coumaroyl- and caffeoyl-D-quinic acid by gas chromatography/mass spectrometry. J Mass Spectrom 31(6):602–608

    Article  CAS  Google Scholar 

  • Gamborg OL, Miller RA, Ojima K (1968) Nutrient requirements of suspension cultures of soybean root cells. Exp Cell Res 50:151–158

    Article  CAS  PubMed  Google Scholar 

  • Gatica-Arias A, Weber G (2013) Genetic transformation of hop (Humulus lupulus L. cv Tettnanger) by particle bombardment and plant regeneration using a temporary immersion system. In Vitro Cell Dev Biol Plant 49:656–664

    Article  CAS  Google Scholar 

  • Gatica-Arias A, Amma N, Stanke M, Weber G (2012) Agrobacterium rhizogenes-mediated transformation of hop (Humulus lupulus L. cv. Tettnanger): establishment of a system for functional evaluation of genes. Brew Sci 65:91–95

    Google Scholar 

  • Gerhäuser C (2009) Phenolic beer compounds to prevent cancer. In: Preedy VR (ed) Beer in health and disease prevention. Elsevier Inc, San Diego, pp 669–684

    Chapter  Google Scholar 

  • Gerhäuser C (2005) Broad spectrum anti-infective potential of xanthohumol from hop (Humulus lupulus L.) in comparison with activities of other hop constituents and xanthohumol metabolites. Mol Nutr Food Res 49(9):827–831

    Article  PubMed  CAS  Google Scholar 

  • Gerhäuser C, Alt A, Heiss E et al (2002) Cancer chemopreventive activity of xanthohumol, a natural product derived from hop. Mol Cancer Ther 1(11):959–969

    PubMed  Google Scholar 

  • Gil-Ramírez A, Mendiola JA, Arranz E et al (2012) Highly isoxanthohumol enriched hop extract obtained by pressurized hot water extraction (PHWE). Chemical and functional characterization. Innov Food Sci Emerg Technol 16:54–60

    Article  CAS  Google Scholar 

  • Gledhill D (2008) The names of plants. Cambridge University Press, Cambridge

    Book  Google Scholar 

  • Goleniowski M, Bonfill M, Cusido R et al (2013) Phenolic acids. In: Ramawat KG, Mérillon JM (eds) Natural products. Springer, Berlin, Heidelberg, pp 1951–1973

    Chapter  Google Scholar 

  • Gorissen H, Bellinck C, Vancraenenbroeck R et al (1968) Separation and identification of (+)-gallocatechine in hops. Arch Int Physiol Biochim 76(5):932–934

    CAS  PubMed  Google Scholar 

  • Green CP (1997) Comparison of tettnanger, saaz, hallertau and fuggle hops grown in the USA, Australia and Europe. J Inst Brew 103:232–243

    Google Scholar 

  • Guo J, Nikolic D, Chadwick LR et al (2006) Identification of human hepatic cytochrome P450 enzymes involved in the metabolism of 8-prenylnaringenin and isoxanthohumol from hops (Humulus lupulus L.). Drug Metab Dispos 34(7):1152–1159

    Article  CAS  PubMed  Google Scholar 

  • Gurriaran MJ, Revilla MA, Tames RS (1999) Adventitious shoot regeneration in cultures of Humulus lupulus L. (hop) cvs. Brewers Gold and Nugget. Plant Cell Rep 18:1007–1011

    Article  CAS  Google Scholar 

  • Hall AJ, Babish JG, Darland GK et al (2008) Safety, efficacy and anti-inflammatory activity of rho iso-alpha-acids from hops. Phytochemistry 69(7):1534–1547

    Article  CAS  PubMed  Google Scholar 

  • Hänsel R, Schulz J (1988) Desmethylxanthohumol: isolierung aus hopfen und cyclisierung zu flavanonen. Arch Pharm 321(1):37–40

    Article  Google Scholar 

  • Hänsel R, Wagener HH (1967) Versuche, sedative-hypnotische Wirkstoffe im Hopfen nachzuweisen. Arzneimittelforschung 17(1):79–81

    PubMed  Google Scholar 

  • Hänsel PB, Wohlfart R, Schmidt H (1982) The sedative-hypnotic principle of hops, 3. Communication: contents of 2-methyl-3-butene-2-ol in hops and hop preparations. Planta Med 45:224–228

    Article  PubMed  Google Scholar 

  • Hanske L, Loh G, Sczesny S et al (2010) Recovery and metabolism of xanthohumol in germ-free and human microbiota-associated rats. Mol Nutr Food Res 54(10):1405–1413

    Article  CAS  PubMed  Google Scholar 

  • Harold FV, Hildebrand RP, Morieson AS et al (1960) Influence of hop oil constituents on the flavour and aroma of beer. J Inst Brew 66:395–398

    Article  CAS  Google Scholar 

  • Harris RE, Casto BC, Harris ZM (2014) Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol 5(4):677–692

    Article  PubMed  PubMed Central  Google Scholar 

  • Hartley RD (1968) Varietal differences in volatile water-soluble fractions of hops (Humulus lupulus L.). Phytochemistry 7(9):1641–1644

    Article  CAS  Google Scholar 

  • Hartley RD, Fawcett CH (1969) The separation and identification of germacratriene (4,10-dimethyl-7-isopropylidene-cyclodeca-4,10-diene) from hops (Humulus lupulus). Phytochemistry 8(9):1793–1796

    Article  CAS  Google Scholar 

  • He X, Fang J, Huang L et al (2015) Sophora flavescens Ait.: traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine. J Ethnopharmacol 172:10–29

    Article  CAS  PubMed  Google Scholar 

  • Heinrich M, Barnes J, Prieto Garcia JM, Gibbons S, Williamson EM (2018) Fundamentals of pharmacognosy and phytotherapy, 3rd edn. Elsevier, London

    Google Scholar 

  • Herath W, Ferreira W, Khan SI et al (2003) Identification and biological activity of microbial metabolites of xanthohumol. Chem Pharm Bull 51(11):1237–1240

    Article  CAS  PubMed  Google Scholar 

  • Hermans-Lokkerbol ACJ, Verpoorte R (1994a) Preparative separation and isolation of three α bitter acids from hop, Humulus lupulus L., by centrifugal partition chromatography. J Chrom A 664(1):45–53

    Article  CAS  Google Scholar 

  • Hermans-Lokkerbol ACJ, Verpoorte R (1994b) Development and validation of a high-performance liquid chromatography system for the analysis of hop bitter acids. J Chrom A 669(1–2):65–73

    Article  CAS  Google Scholar 

  • Hermans-Lokkerbol ACJ, Hoek AC, Verpoorte R (1997) Preparative separation of bitter acids from hop extracts by centrifugal partition chromatography. J Chrom A 771(1–2):71–79

    Article  CAS  Google Scholar 

  • Herraiz T, Galisteo J (2003) Tetrahydro-β-carboline alkaloids occur in fruits and fruit juices. Activity as antioxidants and radical scavengers. J Agric Food Chem 51(24):7156–7161

    Article  CAS  PubMed  Google Scholar 

  • Ho YC, Liu CH, Chen CN et al (2008) Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines. Phytother Res 22(11):1465–1468

    Article  CAS  PubMed  Google Scholar 

  • Horlemann C, Schwekendiek A, Höhnle M et al (2003) Regeneration and agrobacterium-mediated transformation of hop (Humulus lupulus L.). Plant Cell Rep 22:210–217

    Article  CAS  PubMed  Google Scholar 

  • Hornsey IS (2003) A history of beer and brewing. The Royal Society of Chemistry, Cambridge

    Google Scholar 

  • Hudcova T, Bryndova J, Fialova K et al (2014) Antiproliferative effects of prenylflavonoids from hops on human colon cancer cell lines. J Inst Brew 120(3):225–230

    Article  CAS  Google Scholar 

  • Humpel M, Isaksson P, Schaefer O et al (2005) Tissue specificity of 8-prenylnaringenin: protection from ovariectomy induced bone loss with minimal trophic effects on the uterus. J Steroid Biochem 97(3):299–305

    Article  CAS  Google Scholar 

  • Hussong R, Frank N, Knauft J et al (2005) A safety study of oral xanthohumol administration and its influence on fertility in Sprague-Dawley rats. Mol Nutr Food Res 49(9):861–867

    Article  CAS  PubMed  Google Scholar 

  • Igura K, Ohta T, Kuroda Y et al (2001) Resveratrol and quercetin inhibit angiogenesis in vitro. Cancer Lett 171(1):11–16

    Article  CAS  PubMed  Google Scholar 

  • Intelmann D, Haseleu G, Hofmann T (2009) LC-MS/MS quantitation of hop-derived bitter compounds in beer using the ECHO technique. J Agric Food Chem 57(4):1172–1182

    Article  CAS  PubMed  Google Scholar 

  • Itokawa H, Ebata N, Takeya K et al (1980) Studies on the tissue cultures of Humulus lupulus L. and the chemical constituents. Shoyakugaku Zasshi 34:196–199

    CAS  Google Scholar 

  • Jelínek L, Sneberger M, Karabín M et al (2010) Comparison of Czech hop cultivars based on their contents of secondary metabolites. Czech J Food Sci 28(4):309–316

    Article  Google Scholar 

  • Jeong HM, Han EH, ** YH et al (2011) Xanthohumol from the hop plant stimulates osteoblast differentiation by RUNX2 activation. Biochem Biophys Res Commun 409(1):82–89

    Article  CAS  PubMed  Google Scholar 

  • Jerkovic V, Collin S (2007) Occurrence of resveratrol and piceid in American and European hop cones. J Agric Food Chem 55(21):8754–8758

    Article  CAS  PubMed  Google Scholar 

  • Jerkovic V, Collin S (2008) Fate of resveratrol and piceid through different hop processings and storage times». J Agric Food Chem 56(2):584–590

    Article  CAS  PubMed  Google Scholar 

  • Jerkovic V, Callemien D, Collin S (2005) Determination of stilbenes in hop pellets from different cultivars. J Agric Food Chem 53(10):4202–4206

    Article  CAS  Google Scholar 

  • Jirovetz L, Bail S, Buchbauer G et al (2006) Antimicrobial testings, gaz chromatographic analysis and olfactory evaluation of an essential oil of hops cones (Humulus lupulus L.) from Bavaria and some of its main compounds. Sci Pharm 74:189–201

    Article  CAS  Google Scholar 

  • Kang CH, Choi YH, Moon SK et al (2013) Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-kappa B pathway and activating the Nrf2-dependent HO-1 pathway. Int Immunopharmacol 17(3):808–813

    Article  CAS  PubMed  Google Scholar 

  • Karabín M, Jelínek L, Kinčl T et al (2013) New approach to the production of xanthohumol-enriched beers. J Inst Brew 119:98–102

    Google Scholar 

  • Karabín M, Hudcová T, Jelínek L et al (2015) Biotransformations and biological activities of hop flavonoids. Biotechnol Adv 33(6):1063–1090

    Article  PubMed  CAS  Google Scholar 

  • Karabín M, Hudcová T, Jelínek L et al (2016) Biologically active compounds from hops and prospects for their use. Compr Rev Food Sci Food Saf 15(3):542–567

    Article  CAS  Google Scholar 

  • Katsiotis ST, Langezaal CR, Scheffer JJC et al (1989) Comparative study of the essential oils from hops of various Humulus lupulus L. cultivars ». Flavour Fragr J 4:187–191

    Article  CAS  Google Scholar 

  • Keiler AM, Zierau O, Kretzschmar G (2013) Hop extracts and hop substances in treatment of menopausal complaints. Planta Med 79(7):576–579

    Article  CAS  PubMed  Google Scholar 

  • Keiler AM, Helle J, Bader MI et al (2017a) A standardized Humulus lupulus (L.) ethanol extract partially prevents ovariectomy-induced bone loss in the rat without induction of adverse effects in the uterus. Phytomedicine 34:50–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keiler AM, Macejova D, Dietz BM et al (2017b) Evaluation of estrogenic potency of a standardized hops extract on mammary gland biology and on MNU-induced mammary tumor growth in rats. J Steroid Biochem Mol Biol 174:234–241

    Article  CAS  PubMed  Google Scholar 

  • Keller K, Hansel R, Chandler RF (1993) Adverse effects of herbal drugs. Springer, Berlin

    Google Scholar 

  • Killeen D, Watkins OC, Sansom CE et al (2017) Fast sampling, analyses and chemometrics for plant breeding: bitter Acids, xanthohumol and terpenes in lupulin glands of hops (Humulus lupulus). Phytochem Anal 28(1):50–57

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto T, Kobayashi M, Yako N et al (2008) Comparison of 4-mercapto-4-methylpentan-2-one contents in hop cultivars from different growing regions. J Agric Food Chem 56:1051–1057

    Article  CAS  PubMed  Google Scholar 

  • Kiyama R (2016) Biological effects induced by estrogenic activity of lignans. Trends Food Sci Technol 54:186–196

    Article  CAS  Google Scholar 

  • Koetter U, Schrader E, Kaufeler R et al (2007) A randomized, double blind, placebo-controlled, prospective clinical study to demonstrate clinical efficacy of a fixed valerian hops extract combination (Ze 91019) in patients suffering from non-organic sleep disorder. Phytother Res 21(9):847–851

    Article  CAS  PubMed  Google Scholar 

  • Krofta K, Poustka J, Novàkovà K et al (2005) Contents of prenylflavonoids in Czech hops and beers. In: ISHS acta horticulturae 668 at the International Humulus Symposium, Corvallis (Oregon), USA, 1st February 2005

  • Kurasawa T, Chikaraishi Y, Naito A et al (2005) Effect of Humulus lupulus on gastric secretion in a rat pylorus-ligated model. Biol Pharm Bull 28(2):353–357

    Article  CAS  PubMed  Google Scholar 

  • Lammens H, Verzele M (1968) The aroma of hops III. The occurrence of diterpenes in hop oil. Bull Des Soc Chim Belg 77(9–10):497–503

    CAS  Google Scholar 

  • Langezaal CR, Scheffer JJC (1992) Initiation and growth characterization of some hop cell suspension cultures. Plant Cell Tiss Org Cult 30:159–164

    Article  CAS  Google Scholar 

  • Langezaal CR, Chandra A, Scheffer JJC (1992) Antimicrobial screening of essential oils and extracts of some Humulus lupulus cultivars. Pharm Weekbl Sci 14(6):353–356

    Article  CAS  PubMed  Google Scholar 

  • Larson AE, Yu RRY, Lee OA et al (1996) Antimicrobial activity of hop extracts against Listeria monocytogenes in media and in food. Int J Food Microbiol 33(2):195–207

    Article  CAS  PubMed  Google Scholar 

  • Lee JC, Kundu JK, Hwang DM et al (2007) Humulone inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of NF-κB and AP-1: IκB kinase and c-Jun-N-terminal kinase as respective potential upstream targets. Carcinogenesis 28(7):1491–1498

    Article  CAS  PubMed  Google Scholar 

  • Legette L, Ma L, Reed RL et al (2012) Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration. Mol Nutr Food Res 56(3):466–474

    Article  CAS  PubMed  Google Scholar 

  • Legette LL, Luna AYM, Reed RL et al (2013) Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats. Phytochemistry 91:236–241

    Article  CAS  Google Scholar 

  • Legette LC, Karnpracha C, Reed CR et al (2014) Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops. Mol Nutr Food Res 58:248–255

    Article  CAS  PubMed  Google Scholar 

  • Li HJ, Deinzer ML (2006) Structural identification and distribution of proanthocyanidins in 13 different hops. J Agric Food Chem 54(11):4048–4056

    Article  CAS  PubMed  Google Scholar 

  • Li H, Ban Z, Qin H et al (2015) A heteromeric membrane–bound prenyltransferase complex from hop catalyses three sequential aromatic prenylations in the bitter acid pathway. Plant Physiol 167:650–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Li N, Li X et al (2017) Characteristic alpha-acid derivatives from Humulus lupulus with antineuroinflammatory activities. J Nat Prod 80(12):3081–3093

    Article  CAS  PubMed  Google Scholar 

  • Ligor M, Stankevičius M, Wenda-Piesik A et al (2014) Comparative gas chromatographic-mass spectrometric evaluation of hop (Humulus lupulus L.) essential oils and extracts obtained using different sample preparation methods. Food Anal Methods 7:1433–1442

    Article  Google Scholar 

  • Liu M, Yin H, Liu G et al (2014) Xanthohumol, a prenylated chalcone from beer hops, acts as an alpha-glucosidase inhibitor in vitro. J Agr Food Chem 62(24):5548–5554

    Article  CAS  Google Scholar 

  • Lou S, Zheng YM, Liu SL et al (2014) Inhibition of hepatitis C virus replication in vitro by xanthohumol, a natural product present in hops. Planta Med 80(2–3):171–176

    CAS  PubMed  Google Scholar 

  • Lukaczer D, Darland G, Tripp M et al (2005) A pilot trial evaluating Meta050, a proprietary combination of reduced iso-alpha acids, rosemary extract and oleanolic acid in patients with arthritis and fibromyalgia. Phytother Res 19(10):864–869

    Article  CAS  PubMed  Google Scholar 

  • Luzak B, Golanski J, Przygodzki T et al (2016) Extract from spent hop (Humulus lupulus L.) reduces blood platelet aggregation and improves anticoagulant activity of human endothelial cells in vitro. J Funct Foods 22:257–269

    Article  CAS  Google Scholar 

  • Mabberley DJ (2008) Mabberley’s plant-book: a portable dictionary of plants, their classification and uses. Cambridge University Press, Cambridge

    Google Scholar 

  • Magalhães PJ, Guido LF, Cruz JM et al (2007) Analysis of xanthohumol and isoxanthohumol in different hop products by liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry. J Chrom A 1150(1–2):295–301

    Article  CAS  Google Scholar 

  • Magalhães PJ, Vieira JS, Gonçalves LM et al (2010) Isolation of phenolic compounds from hop extracts using polyvinylpolypyrrolidone: characterization by high-performance liquid chromatography–diode array detection–electrospray tandem mass spectrometry. J Chromatogr A 1217(19):3258–3268

    Article  PubMed  CAS  Google Scholar 

  • Maietti A, Brighenti V, Bonetti G et al (2017) Metabolite profiling of flavonols and in vitro antioxidant activity of young shoots of wild Humulus lupulus L. (hop). J Pharm Biomed Anal 142:28–34

    Article  CAS  PubMed  Google Scholar 

  • Malizia RA, Molli JS, Cardell DA et al (1999) Essential oil of hop cones (Humulus lupulus L.). J Essent Oil Res 11(1):13–15

    Article  CAS  Google Scholar 

  • Maroo N, Hazra A, Das T (2013) Efficacy and safety of a polyherbal sedative-hypnotic formulation NSF-3 in primary insomnia in comparison to zolpidem: a randomized controlled trial. Indian J Pharmacol 45(1):34–39

    Article  PubMed  PubMed Central  Google Scholar 

  • Matousek J, Kocabek T, Patzak J et al (2010) Cloning and molecular analysis of HIbZip1 and HIbZip2 transcription factors putatively involved in the regulation of the lupulin metabolome in hop (Humulus lupulus L.). J Agric Food Chem 58:902–912

    Article  CAS  PubMed  Google Scholar 

  • Matousek J, Kocabek T, Patzak J et al (2016) The “putative” role of transcription factors from HlWRKY family in the regulation of the final steps of prenylflavonoid and bitter acids biosynthesis in hop (Humulus lupulus L.). Plant Mol Biol 92:263–277

    Article  CAS  PubMed  Google Scholar 

  • Matoušek J, Vrba L, Novák P et al (2005) Cloning and molecular analysis of the regulatory factor HlMyb1 in hop (Humulus lupulus L.) and the potential of hop to produce bioactive prenylated flavonoids. J Agric Food Chem 53(12):4793–4798

    Article  PubMed  CAS  Google Scholar 

  • Maye JP, Smith R, Leker J (2016) Humulinone formation in hops and hop pellets and its implications for dry hopped beers. MBAA TQ 53(1):23–27

    Google Scholar 

  • Meissner O, Haberlein H (2006) Influence of xanthohumol on the binding behavior of GABA(A) receptors and their lateral mobility at hippocampal neurons. Planta Med 72(7):656–658

    Article  CAS  Google Scholar 

  • Milligan SR, Kalita JC, Heyerick A et al (1999) Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 84(6):2249–2252

    Article  CAS  PubMed  Google Scholar 

  • Milligan SR, Kalita JC, Pocock V et al (2000) The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocr Metab 85(12):4912–4915

    Article  CAS  PubMed  Google Scholar 

  • Minich DM, Bland JS, Katke J et al (2007) Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid for inflammatory conditions. Can J Physiol Pharmacol 85(9):872–883

    Article  CAS  PubMed  Google Scholar 

  • Miranda CL, Stevens JF, Helmrich A et al (1999) Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem Toxicol 37:271–285

    Article  CAS  PubMed  Google Scholar 

  • Miranda CL, Stevens JF, Ivanov V et al (2000) Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones in vitro. J Agric Food Chem 48(9):3876–3884

    Article  CAS  PubMed  Google Scholar 

  • Mizobuchi S, Sato Y (1984) A new flavanone with antifungal activity isolated from hops. Agric Biol Chem 48:2771–2775

    CAS  Google Scholar 

  • Mizobuchi S, Sato Y (1985) Antifungal activities of hop bitter resins and related compounds. Agric Biol Chem 49(2):399–403

    CAS  Google Scholar 

  • Mockute D, Bernotienė G, Nivinskiene O et al (2008) Variability of volatiles of wild hops (Humulus lupulus L) growing in eastern Lithuania. J Essent Oil Res 20(2):96–101

    Article  CAS  Google Scholar 

  • Moir M, Seaton JC, Suggett A (1980a) 2,3,5-Trithiahexane in the essential oil of Humulus lupulus. Phytochemistry 19(10):2201

    Article  CAS  Google Scholar 

  • Moir M, Gallacher IM, Hobkirk J et al (1980b) Methylthiomethyl 2-methylbutanethiolate in essential oil of hop. Tetrahedron Lett 21(11):1085–1086

    Article  CAS  Google Scholar 

  • Monteiro R, Faria A, Azevedo I et al (2007) Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavonoids. J Steroid Biochem 105(1–5):124–130

    Article  CAS  Google Scholar 

  • Monzote L, Lackova A, Staniek K et al (2017) The antileishmanial activity of xanthohumol is mediated by mitochondrial inhibition. Parasitology 144(6):747–759

    Article  CAS  PubMed  Google Scholar 

  • Morin CM, Koetter U, Bastien C et al (2005) Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep 28(11):1465–1471

    Article  PubMed  Google Scholar 

  • Mouratidis PXE, Colston KW, Tucknott ML et al (2013) An investigation into the anticancer effects and mechanism of action of hop β-acid lupulone and its natural and synthetic derivatives in prostate cancer cells. Nutr Cancer 65(7):1086–1092

    Article  CAS  PubMed  Google Scholar 

  • Murakami A, Darby P, Javornik B et al (2006) Molecular phylogeny of wild Hops, Humulus lupulus. Heredity 97:66–74

    Article  CAS  PubMed  Google Scholar 

  • Murashige T, Skoog F (1962) A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant 15:437–497

    Article  Google Scholar 

  • Nagel J, Culley LK, Lu Y et al (2008) EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol. Plant Cell 20(1):186–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nance MR, Setzer WN (2011) Volatile components of aroma hops (Humulus lupulus L.) commonly used in beer brewing. J Brew Distilling 2(2):16–22

    CAS  Google Scholar 

  • Natarajan P, Katta S, Andrei I et al (2008) Positive antibacterial co-action between hop (Humulus lupulus) constituents and selected antibiotics. Phytomedicine 15:194–201

    Article  CAS  PubMed  Google Scholar 

  • Natsume S, Takagi H, Shiraishi A et al (2015) The draft genome of hop (Humulus lupulus), an essence for brewing. Plant Cell Physiol 56:428–441

    Article  CAS  PubMed  Google Scholar 

  • Naya Y, Kotake M (1969a) Natural occurrence of humulol and tricyclohumuladiol. Bull Chem Soc Jpn 42(8):2405

    Article  CAS  Google Scholar 

  • Naya Y, Kotake M (1969b) Natural occurrence of α-cadinene. Bull Chem Soc Jpn 42(5):1468

    Article  CAS  Google Scholar 

  • Naya Y, Kotake M (1969c) Natural Occurrence of humuladienone, humulenone-II, and α-corocalene; new constituents of hop oil ». Bull Chem Soc Jpn 42(7):2088

    Article  CAS  Google Scholar 

  • Negrao R, Duarte D, Costa R et al (2013) Isoxanthohumol modulates angiogenesis and inflammation via vascular endothelial growth factor receptor, tumor necrosis factor alpha and nuclear factor kappa B pathways. BioFactors 39(6):608–622

    Article  CAS  PubMed  Google Scholar 

  • Negri G, di Santi D, Tabach R (2010) Bitter acids from hydroethanolic extracts of Humulus lupulus L., Cannabaceae, used as anxiolytic. Rev Bras Farmacogn 20(6):850–859

    Article  CAS  Google Scholar 

  • Nikolic D, Li Y, Chadwick LR et al (2004) Metabolism of 8-prenylnaringenin, a potent phytoestropgen from hops, Humulus lupulus, by human liver microsomes. Drug Metab Disp 32:272–279

    Article  CAS  Google Scholar 

  • Nookandesh A, Frank N, Steiner F et al (2004) Xanthohumol metabolites in faeces of rats. Phytochemistry 65(5):561–570

    Article  CAS  Google Scholar 

  • Nozawa H, Nakao W, Zhao F et al (2005) Dietary supplement of isohumulones inhibits the formation of aberrant crypt foci with a concomitant decrease in prostaglandin E2 level in rat colon. Mol Nutr Food Res 49:772–778

    Article  CAS  PubMed  Google Scholar 

  • Oberbauer E, Urmann C, Steffenhagen C et al (2013) Chroman-like cyclic prenylflavonoids promote neuronal differentiation and neurite outgrowth and are neuroprotective. J Nutr Biochem 24:1953–1962

    Article  CAS  PubMed  Google Scholar 

  • Ohsugi M, Basnet P, Kadota S et al (1997) Antibacterial activity of traditional medicines and an active constituent lupulone from H. lupulus against Helicobacter pylori. J Trad Med 14:186–191

    CAS  Google Scholar 

  • Okada Y, Saeki K, Inaba A et al (2003) Construction of gene expression system in hop (Humulus lupulus) lupulin gland using valerophenone synthase promoter. J Plant Physiol 160:1101–1108

    Article  CAS  PubMed  Google Scholar 

  • Oladokun O, Tarrega A, James S et al (2016) The impact of hop bitter acid and polyphenol profiles on the perceived bitterness of beer. Food Chem 205:212–220

    Article  CAS  PubMed  Google Scholar 

  • Olšovská J, Kameník Z, Čejka P et al (2013) Ultra-high-performance liquid chromatography profiling method for chemical screening of proanthocyanidins in Czech hops. Talanta 116:919–926

    Article  PubMed  CAS  Google Scholar 

  • Overk CR, Guo J, Chadwick LR et al (2008) In vivo estrogenic comparisons of Trifolium pratense (red clover), Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin. Chem Biol Interact 176(1):30–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Overk CR, Yao P, Chadwick LR et al (2005) Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J Agric Food Chem 53:6246–6253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pal Sing I, Bharate SB (2006) Phloroglucinol compounds of natural origin. Nat Prod Rep 23(4):558–591

    Article  CAS  Google Scholar 

  • Pang Y, Nikolic D, Zhu D et al (2007) Binding of the hop (Humulus lulupus L.) chalcone xanthohumol to cytosolic proteins in Caco-2 intestinal epithelial cells. Mol Nutr Food Res 51:872–879

    Article  CAS  PubMed  Google Scholar 

  • Peacock VE, McCarty P (1992) Varietal identification of hops and hop pellets. MBAA 29(3):81–85

    CAS  Google Scholar 

  • Peppard TL, Sharpe FR (1977) 2,3,4-Trithiapentane in the essential oil from Humulus lupulus. Phytochemistry 16(12):2020–2021

    Article  CAS  Google Scholar 

  • Possemiers S, Verstraete W (2009) Oestrogenicity of prenylflavonoids from hops: activation of pro-oestrogens by intestinal bacteria. Environ Microbiol Rep 1(2):100–109

    Article  CAS  PubMed  Google Scholar 

  • Possemiers S, Heyerick A, Robbens V et al (2005) Activation of proestrogens from hops (Humulus lupulus L.) by intestinal microbiota; conversion of isoxanthohumol into 8-prenylnaringenin. J Agric Food Chem 53(16):6281–6288

    Article  CAS  PubMed  Google Scholar 

  • Possemiers S, Bolca S, Grootaert C et al (2006) The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human instestine. J Nutr 136(7):1862–1867

    Article  CAS  PubMed  Google Scholar 

  • Power FB, Tutin F, Rogerson H (1913) The constituents of hops. J Chem Soc 103:1267–1292

    Article  CAS  Google Scholar 

  • Praet T, Opstaele FV, Steenackers B et al (2015) Changes in the hop-derived volatile profile upon lab scale boiling. Food Res Int 75:1–10

    Article  CAS  PubMed  Google Scholar 

  • Prencipe F, Brighenti V, Rodolfi M et al (2014) Development of a new high-performance liquid chromatography method with diode array and electrospray ionization-mass spectrometry detection for the metabolite fingerprinting of bioactive compounds in Humulus lupulus L. J Chrom A 1349:50–59

    Article  CAS  Google Scholar 

  • Psenakova I, Gasparkova L, Farago J (2009) Polyphenol and flavonoid contents of hop callus and cell suspension cultures. Proc Sci Com IHGC Leon Spain, 109

  • Rad M, Hümpel M, Scharfer O et al (2006) Pharmacokinetics and systemic endocrine effects of the phyto-estrogen 8-prenylnaringenin after single oral doses to postmenopausal women. Br J Clin Pharmacol 62(3):288–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakouski S, Matousek J (1994) Direct organogenesis in hop-a prerequisite for an application of A. tumefaciens-mediated transformation. Biol plantarum 36:191–200

    Article  Google Scholar 

  • Rancán L, Paredes SD, García I et al (2017) Protective effect of xanthohumol against age-related brain damage. J Nutr Biochem 49:133–140

    Article  PubMed  CAS  Google Scholar 

  • Rillaers G, Verzele M (1962) Prehumulone, a new α-acid. Bull Soc Chim Belg 71:438–445

    Article  CAS  Google Scholar 

  • Robins RJ, Furze JM, Rhodes MJC (1985) α-acid degradation by suspension culture cells of Humulus lupulus. Phytochem 24:709–714

    Article  CAS  Google Scholar 

  • Rossini F, Loreti P, Provenzano ME et al (2016) Agronomic performance and beer quality assessment of twenty hop cultivars grown in Central Italy. Int J Agron 11:746–753

    Google Scholar 

  • Roy AT, Leggett G, Koutoulis A (2001) Development of a shoot multiplication system for hop (Humulus lupulus L.). In Vitro Cell Dev Biol Plant 37:79–83

    Article  CAS  Google Scholar 

  • Rozalski M, Micota B, Sadowska B et al (2013) Antiadherent and antibiofilm activity of Humulus lupulus L derived products: new pharmacological properties. Biomed Res Int 2013:101089

    Article  PubMed  PubMed Central  Google Scholar 

  • Sagesser M, Deinzer M (1996) HPLC-ion spray-tandem mass spectrometry of flavonol glycosides in Hops. J Am Soc Brew Chem 54(3):129–134

    Google Scholar 

  • Sakamoto K, Konings WN (2003) Beer spoilage bacteria and hops resistance. Int J Food Microbiol 89(2–3):105–124

    Article  CAS  PubMed  Google Scholar 

  • Saldivar JS, Lopez D, Feldman RA et al (2007) COX-2 overexpression as a biomarker of early cervical carcinogenesis: a pilot study. Gynecol Oncol 107(1):S155–S162

    Article  CAS  PubMed  Google Scholar 

  • Sandoval-Ramirez BA, Lamuela-Raventos RM, Estruch E et al (2017) Beer polyphenols and menopause: effects and mechanisms—a review of current knowledge. Oxid Med Cell Longev 2017:9p

    Article  Google Scholar 

  • Sansawat T, Lee HC, Zhan L et al (2016) Antilisterial effects of different hop acids in combination with potassium acetate and potassium diacetate at 7 and 37 °C. Food Control 59:256–261

    Article  CAS  Google Scholar 

  • Schiller H, Forster A, Vonhoff C, Hegger M, Biller A, Winterhoff H (2006) Sedating effects of Humulus lupulus L. extracts. Phytomedicine 13(8):535–541

    Article  CAS  PubMed  Google Scholar 

  • Schläger S, Dräger B (2016) Exploiting plant alkaloids. Curr Opin Biotechnol 37:155–164

    Article  PubMed  CAS  Google Scholar 

  • Schmalreck AF, Teuber M (1975) Structural features determining the antibiotic potencies of natural and synthetic hop bitter resins, their precursors and derivatives. Can J Microbiol 21(2):205–212

    Article  CAS  PubMed  Google Scholar 

  • Schmandke H (2010) Prenylflavonoids in hops and beer—biochemical activities. Ernahrungs –. Umschau 53(6):225–229

    Google Scholar 

  • Segawa S, Yasui K, Takata Y et al (2006) Flavonoid glycosides extracted from hop (Humulus lupulus L.) as inhibitors of chemical mediator release from human basophilic KU812 cells. Biosci Biotechnol Biochem 70(12):2990–2997

    Article  CAS  PubMed  Google Scholar 

  • Segawa S, Yasui K, Takata Y et al (2014) Flavonoid glycosides extracted from hop (Humulus lupulus L.) as inhibitors of chemical mediator release from human basophilic KU812 cells. Biosci Biotechnol Biochem 70(12):2990–2997

    Article  CAS  Google Scholar 

  • Seliger JM, Misuri L, Maser E et al (2018) The hop-derived compounds xanthohumol, isoxanthohumol and 8-prenylnaringenin are tight-binding inhibitors of human aldo-keto reductases 1B1 and 1B10. J Enzyme Inhib Med Chem 33(1):607–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Semwal DK, Semwal RB, Combrinck S et al (2016) Myricetin: a dietary molecule with diverse biological activities. Nutrients 90(8):2–31

    Google Scholar 

  • Sharp D (2016) Factors that influence the Aroma and Monoterpene Alcohol Profile of Hopped Beer. Dissertation, Oregon State University

  • Sharpe FR, Laws DRJ (1981) The essential oil of hops a Review. J Inst Brew 87(2):96–107

    Article  CAS  Google Scholar 

  • Shimura M, Hasumi A, Minato T et al (2005) Isohumulones modulate blood lipid status through the activation of PPAR alpha. Biochim Biophys Acta 1736(1):51–60

    CAS  PubMed  Google Scholar 

  • Simpson MG (2010) Plant systematics, 2nd edn. Academic, Burlington

    Google Scholar 

  • Simpson WJ, Smith AR (1992) Factors affecting antibacterial activity of hop compounds and their derivatives. J Appl Bacteriol 72(4):327–334

    Article  CAS  PubMed  Google Scholar 

  • Skof S, Luthar Z (2005) Detection of the reporter and selection genes in transformed hop (Humulus lupulus L.). Acta Agric Sloven 85:351–358

    CAS  Google Scholar 

  • Smykalova I, Ortova M, Lipavska H et al (2001) Efficient in vitro micropropagation and regeneration of Humulus lupulus on low sugar, starch-Gelrite media. Biol Plantarum 44:7–12

    Article  CAS  Google Scholar 

  • Soderberg U, Wachtmeister C (1955) Pharmacological effects of humulone on cats and rabbits. Acta Physiol Scand 34(1):90–98

    Article  CAS  PubMed  Google Scholar 

  • Song-San S, Watanabe S, Saito T (1989) Chalcones from Humulus lupulus. Phytochemistry 28(6):1776–1777

    Article  Google Scholar 

  • Spetsig LO, Steninger M (1960) Hulupones, a new group of hop bitter substances. J Inst Brew 66(5):413–417

    Article  CAS  Google Scholar 

  • Spiewak R, Gora A, Dutkiewicz J (2001) Work-related skin symptoms and type I allergy among eastern-Polish farmers growing hops and other crops. Ann Agric Environ Med 8(1):51–56

    CAS  PubMed  Google Scholar 

  • Srinivasan V, Goldberg D, Haas GJ (2004) Contributions to the antimicrobial spectrum of hop constituents. Econ Bot 58(1):230–238

    Article  Google Scholar 

  • Sterba K, Cejka P, Culik J et al (2015) Determination of linalool in different hop varieties using a new method based on fluidized-bed extraction with gas chromatographic-mass spectrometric detection. J Am Soc Brew Chem 73(2):151–158

    CAS  Google Scholar 

  • Stevens R (1967) The chemistry of hop constituents. Chem Rev 67(1):19–71

    Article  CAS  Google Scholar 

  • Stevens JF, Page JE (2004) Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry 65(10):1317–1330

    Article  CAS  Google Scholar 

  • Stevens R, Wright D (1963) The chemistry of hop constituents. Part XV. Tetrahydrocohulupone. J Chem Soc 329:1763-1768

  • Stevens R, Wright D (1963b) The chemistry of hop constituents. Part XV. Tetrahydrocohulupone. J Chem Soc 329:1763–1768

    Article  Google Scholar 

  • Stevens JF, Ivancic M, Hsu VL et al (1997) Prenylflavonoids from Humulus lupulus. Phytochemistry 44(8):1575–1585

    Article  CAS  Google Scholar 

  • Stevens JF, Taylor AW, Deinzer ML (1999) Quantitative analysis of xanthohumol and related prenylflavonoids in hops and beer by liquid chromatography–tandem mass spectrometry. J Chrom A 832(1–2):97–107

    Article  CAS  Google Scholar 

  • Stevens JF, Taylor AW, Nickerson GB et al (2000) Prenylflavonoid variation in Humulus lupulus: distribution and taxonomic significance of xanthogalenol and 4′-O-methylxanthohumol. Phytochemistry 53(7):759–775

    Article  CAS  PubMed  Google Scholar 

  • Stevens JF, Miranda CL, Wolthers KR et al (2002) Identification and in vitro biological activities of hop proanthocyanidins: inhibition of NNOS activity and scavenging of reactive nitrogen species. J Agric Food Chem 50(12):3435–3443

    Article  CAS  PubMed  Google Scholar 

  • Suh KS, Rhee SY, Kim YS et al (2013) Xanthohumol modulates the expression of osteoclast-specific genes during osteoclastogenesis in RAW264.7 cells. Food Chem Toxicol 62:99–106

    Article  CAS  PubMed  Google Scholar 

  • Sumiyoshi M, Kimura Y (2013) Hop (Humulus lupulus L.) extract inhibits obesity in mice fed a high-fat diet over the long term. Br J Nutr 109(1):162–172

    Article  CAS  PubMed  Google Scholar 

  • Tabata N, Ito M, Tomoda H et al (1997) Xanthohumols, diacylglycerol acyltransferase inhibitors, from Humulus lupulus. Phytochemistry 46(4):683–687

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Honma D, Tamura M et al (2012) New chromanone and acylphloroglucinol glycosides from the bracts of hops. Phytochem Lett 5(3):514–518

    Article  CAS  Google Scholar 

  • Tanaka Y, Yanagida A, Komeya S et al (2014) Comprehensive separation and structural analyses of polyphenols and related compounds from bracts of hops (Humulus lupulus L.). J Agric Food Chem 62(10):2198–2206

    Article  CAS  PubMed  Google Scholar 

  • Taniguchi Y, Matsukura Y, Ozaki H et al (2013) Identification and quantification of the oxidation products derived from α-acids and β-acids during storage of hops (Humulus lupulus L.). J Agric Food Chem 61(12):3121–3130

    Article  CAS  PubMed  Google Scholar 

  • Taniguchi Y, Taniguchi H, Yamada M et al (2014) Analysis of the components of hard resin in hops (Humulus lupulus L.) and structural elucidation of their transformation products formed during the brewing process ». J Agric Food Chem 62(47):11602–11612

    Article  CAS  PubMed  Google Scholar 

  • Tatsis EC, O’Connor SE (2016) New developments in engineering plant metabolic pathways. Curr Opin Biotechnol 42:126–132

    Article  CAS  PubMed  Google Scholar 

  • Teng Y, Li X, Yang K et al (2017) Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers. Eur J Med Chem 125:335–345

    Article  CAS  PubMed  Google Scholar 

  • Teponno RB, Kusari S, Spiteller M (2016) Recent advances in research on lignans and neolignans. Nat Prod Rep 33(9):1044–1092

    Article  CAS  PubMed  Google Scholar 

  • The Plant List (2013). http://www.theplantlist.org. Cited 30 Jan 2018

  • Tobe H, Muraki Y, Kitamura K et al (1997) Bone resorption inhibitors from hop extract. Biosci Biotech Biochem 61(1):158–159

    Article  CAS  Google Scholar 

  • Trevisan MTS, Scheffer JJC, Verpoorte R (1997) Effect of elicitation on the peroxydase activity in some cell suspension cultures of hop, Humulus lupulus. Plant Cell Tissue Organ Cult 48:121–126

    Article  CAS  Google Scholar 

  • Tsurumaru Y, Sasaki K, Miyawaki T et al (2012) HIPT-1, a membrane-bound prenyltransferase responsible for the biosynthesis of bitter acids in hops. Biochem Biophys Res Commun 417(1):393–398

    Article  CAS  PubMed  Google Scholar 

  • Tynan TJ (1989) Synthesis and characterisation of hop derived compounds, and their application in quantitative high performance liquid chromatography. Master of Sciences thesis, Dublin City University

  • Tyrrell E, Archer R, Skinner GA et al (2010) Structure elucidation and an investigation into the in vitro effects of hop acids on human cancer cells. Phytochem Lett 3(1):17–23

    Article  CAS  Google Scholar 

  • Tyrrell E, Archer R, Tucknott M et al (2012) The synthesis and anticancer effects of a range of natural and unnatural hop β-acids on breast cancer cells. Phytochem Lett 5(1):144–149

    Article  CAS  Google Scholar 

  • USDA, United States Department of Agriculture (2017) National hop report

  • Van Breemen RB, Yuan Y, Banuvar S et al (2014) Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops. 58(10):1962–1969

    Google Scholar 

  • Van Cleemput M, Heyerick A, Libert C et al (2009a) Hop bitter acids efficiently block inflammation independent of GRα, PPARα, or PPARγ. Mol Nutr Food Res 53(9):1143–1155

    Article  PubMed  CAS  Google Scholar 

  • Van Cleemput M, Cattoor K, De Bosscher K et al (2009b) Hop (Humulus lupulus)-derived bitter acids as multipotent bioactive compounds. J Nat Prod 72(6):1220–1230

    Article  PubMed  CAS  Google Scholar 

  • Van Opstaele F, Praet T, Aerts G et al (2013) Characterization of novel single-variety oxygenated sesquiterpenoid hop oil fractions via headspace solid-phase microextraction and gas chromatography–mass spectrometry/olfactometry. J Agric Food Chem 61(44):10555–10564

    Article  PubMed  CAS  Google Scholar 

  • Venturelli S, Burkard M, Biendl M et al (2016) Prenylated chalcones and flavonoids for the prevention and treatment of cancer. Nutrition 32:1171–1178

    Article  CAS  PubMed  Google Scholar 

  • Verzele M (1986) 100 years of hop chemistry and its relevance to brewing. J Inst Brew 92(1):32–48

    Article  CAS  Google Scholar 

  • Vlaanderen (1858) Jaresbericht für Chemie 448

  • von Bingen H (2005) Heilkraft der Natur “Physica”. Das Buch von dem inneren Wesen der verschiedenen Naturen der Geschöpfe. Stein am Rhein: Basler Hildegard-Gesellschaft

  • Wang Q, Ding ZH, Liu JK et al (2004) Xanthohumol, a novel anti-HIV-1 agent purified from hops Humulus lupulus. Antivir Res 64:189–194

    CAS  PubMed  Google Scholar 

  • Wang G, Tian L, Aziz N et al (2008) Terpene biosynthesis in glandular trichomes of hop. Plant Physiol 148(3):1254–1266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Zhang YD, Ming W et al (2017) Xanthohumol promotes neuronal and behavioral recovery by suppressing inflammatory response and apoptosis in a rat model of intracerebral hemorrhage. Int J Clin Exp Med 10(5):7843–7850

    CAS  Google Scholar 

  • Wohlfart R, Hänsel PB, Schmidt H (1983a) The sedative-hypnotic principle of hops, 4. Communication: pharmacology of 2-methyl-3-butene-2-ol. Planta Med 48:120–123

    Article  CAS  PubMed  Google Scholar 

  • Wohlfart R, Wurm G, Hänsel PB, Schmidt H (1983b) Detection of sedative hypnotic constituents. Part 5. Degradation of humulones and lupulones to 2-methyl-3-butene-2-ol, a hop constituent possessing sedative hypnotic activity. Arch Pharm (Weinheim) 316:132–137

    Article  CAS  Google Scholar 

  • Yajima H, Ikeshima E, Shiraki M et al (2004) Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. J Biol Chem 279(32):33456–33462

    Article  CAS  PubMed  Google Scholar 

  • Yajima H, Noguchi T, Ikeshima E et al (2005) Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents. Int J Obesity 29(8):991–997

    Article  CAS  Google Scholar 

  • Yamamoto K, Wang J, Yamamoto S et al (2000) Suppression of cyclooxygenase-2 gene transcription by humulone of beer hop extract studied with reference to glucocorticoid. FEBS Lett 465(2–3):103–106

    Article  CAS  PubMed  Google Scholar 

  • Yang M, Li N, Li F et al (2013) Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri. Int Immunopharmacol 16:466–474

    Article  CAS  PubMed  Google Scholar 

  • Yasukawa K, Yamaguchi A, Arita J et al (1993) Inhibitory effect of edible plant-extracts on 12-0-tetradecanoylphorbol-13-acetate-induced ear edema in mice. Phytoter Res 7(2):185–189

    Article  CAS  Google Scholar 

  • Yen TL, Hsu CK, Lu WJ et al (2012) Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats. J Agric Food Chem 60(8):1937–1944

    Article  CAS  PubMed  Google Scholar 

  • Yong WK, Ho YF, Malek SN (2015) Xanthohumol induces apoptosis and S phase cell cycle arrest in A549 non-small cell lung cancer cells. Pharmacogn Mag 11(Suppl2):275–283

    CAS  Google Scholar 

  • Yu L, Zhang F, Hu Z et al (2014) Novel prenylated bichalcone and chalcone from Humulus lupulus and their quinone reductase induction activities. Fitoterapia 93:115–120

    Article  CAS  PubMed  Google Scholar 

  • Zanoli P, Zavatti M (2008) Pharmacognostic and pharmacological profile of Humulus lupulus L. J Ethnopharmacol 116(3):383–396

    Article  CAS  Google Scholar 

  • Zanoli P, Rivasi M, Zavatti M et al (2005) New insight in the neuropharmacological activity of Humulus lupulus L. J Ethnopharmacol 102(1):102–106

    Article  CAS  Google Scholar 

  • Zanoli P, Zavatti M, Rivasi M et al (2007) Evidence that the beta-acids fraction of hops reduces central GABAergic neurotransmission. J Ethnopharmacol 109(1):87–92

    Article  CAS  Google Scholar 

  • Zhang X, Liang X, **ao H et al (2004) Direct characterization of bitter acids in a crude hop extract by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. J Am Soc Mass Spectrom 15(2):180–187

    Article  CAS  PubMed  Google Scholar 

  • Zhang N, Liu ZW, Han QY et al (2009) Inhibition of bovine viral diarrhea virus in vitro by xanthohumol: comparisons with ribavirin and interferon-alpha and implications for the development of anti-hepatitis C virus agents. Eur J Pharm Sci 38(4):332–340

    Article  CAS  PubMed  Google Scholar 

  • Zhang N, Liu ZW, Han QY et al (2010) Xanthohumol enhances antiviral effect of interferon alpha-2b against bovine viral diarrhea virus, a surrogate of hepatitis C virus. Phytomedicine 17(5):310–316

    Article  CAS  PubMed  Google Scholar 

  • Zhang JW, Li PY, Wang XP (2017) Beneficial effect of xanthohumol, a prenylated flavanoid, on 3-nitropropionic acid Induced Huntington’s disease in a rat model. Lat Am J Pharm 36(9):1867–1874

    Google Scholar 

  • Zhao F, Watanabe Y, Nozawa H et al (2005) Prenylflavonoids and phloroglucinol derivatives from hops (Humulus lupulus). J Nat Prod 68(1):43–49

    Article  CAS  PubMed  Google Scholar 

  • Zhao XQ, Jiang K, Liang B et al (2016) Anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-kappa B/p53-apoptosis signaling pathway. Oncol Rep 35:669–675

    Article  CAS  PubMed  Google Scholar 

  • Zierau O, Gester S, Schwab P et al (2002) Estrogenic activity of the phytoestrogens naringenin, 6-(1,1-dimethylallyl)naringenin and 8-prenylnaringenin. Planta Med 68(5):449–451

    Article  CAS  PubMed  Google Scholar 

  • Żołnierczy AK, Mączka WK, Grabarczyk M et al (2015) Isoxanthohumol—biologically active hop flavonoid. Fitoterapia 103:71–82

    Article  CAS  Google Scholar 

  • Zuurbier KWN, Fung SY, Scheffer JJC et al (1995) Formation of aromatic intermediates in the biosynthesis of bitter acids in Humulus lupulus. Phytochemistry 38(1):77–82

    Article  CAS  Google Scholar 

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Acknowledgements

This work has been carried out in the framework of Alibiotech project which is financed by European Union, French State and the French Region of Hauts-de-France. The authors gratefully thank the Region Hauts-de-France and the University of Lille 2 for the funding of the Ph.D. fellow Laetitia Bocquet.

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  1. Univ. Lille, INRA, ISA, Univ. Artois, Univ. Littoral Côte d’Opale, EA 7394, Institut Charles Viollette (ICV), Lille, France

    L. Bocquet, S. Sahpaz, J. L. Hilbert, C. Rambaud & C. Rivière

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  1. L. Bocquet
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  2. S. Sahpaz
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  3. J. L. Hilbert
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  4. C. Rambaud
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  5. C. Rivière
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Correspondence to C. Rivière.

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Bocquet, L., Sahpaz, S., Hilbert, J.L. et al. Humulus lupulus L., a very popular beer ingredient and medicinal plant: overview of its phytochemistry, its bioactivity, and its biotechnology. Phytochem Rev 17, 1047–1090 (2018). https://doi.org/10.1007/s11101-018-9584-y

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