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Plant Profiler

Hops (Humulus lupulus)


Synonyms / Common Names / Related Terms
Colupulone, common hops, European hops, hop, hop strobile, Hopfen (German), houblon (French), humulon, humulus, Humulus lupulus, iso-alpha-acids, lupulin, lupulus, Lupuli strobulus (German), prenylated 2`-hydroxychalcones, prenylflavonoids, spent hops, xanthohumol, Ze 91019.





Mechanism of Action
Pharmacology:
  • Constituents: The volatile oils of hops have been associated with the promotion of sleep and with anti-microbial properties in vitro. The bitter acids may possess anti-inflammatory and anti-proliferative activity and the flavonoids may also have anti-proliferative properties. Xanthohumol is the principal prenylated flavonoid of the female inflorescences of the hop plant. It has been characterized as a "broad spectrum" cancer chemopreventative agent in in vitro studies.4
  • Anti-inflammatory effects: Humulon, one of the bitter constituents in the hop, has shown anti-inflammatory activity in mice by inhibiting activity against 12-O-tetradecanopyphorbo-13-acetate (TPA)-induced inflammation and arachidonic acid-induced inflammation.2
  • Antimicrobial effects: In vitro, the essential oil and chloroform extracts of hops have demonstrated activity against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and fungi (Trichophyton mentagrophytes var. interdigitale).1 Another study found that antibacterial effects associated with weak acids derived from hops increase with decreasing pH.15
  • Antioxidant effects: Prenylated 2`-hydroxychalcones and flavanones from the inflorescences of the female hop plant were shown to inhibit peroxynitrite-mediated oxidation of low-density lipoproteins (LDL). They are mainly found in beer, which contains up to 4mg/L of these polyphenols.19
  • Antiproliferative activity: The bitter acids of hops may possess anti-proliferative activity, and the flavonoids may also have anti-proliferative properties. Hops have been characterized as a "broad spectrum" cancer chemopreventative agent in in vitro studies.4
  • Cytochrome P450 effects: Hop flavonoids have been shown to be effective and selective inhibitors of the human cytochrome P450 enzymes implicated in the activation of carcinogens.16,17 These results are corroborated by an in vivo study demonstrating hops-mediated induction of P450 3A and P450 2B.18 The induction of hepatic cytochrome P450 3A is attributed to the lupulone constituent of hops. The hops component 8-prenylnaringenin has been shown to be a potent inhibitor of the 2-amino-3-methylimidazo[4.5-f] quinoline (IQ), a potential carcinogen found in cooked foods that requires initial metabolic activation by P450.20
  • Glucose metabolism effects: Colupulone from hops has been found to elevate serum glucose levels in diabetic mice, but it has also been shown to have either no effect or to lower serum glucose levels in non-diabetic mice.12,13 In other mouse studies, hops have not significantly altered the parameters of glucose homeostasis (basal glucose and insulin, insulin-induced hypoglycemia, glycated hemoglobin, and pancreatic insulin concentration).14 Isohumulones (isohumulone and isocohumulone), bitter acids derived from hops, activate both peroxisome proliferator-activated receptors alpha and gamma and reduce insulin resistance.21
  • Hormonal effects: Zenisek et al. reported a high level of estrogenic activity in the beta-bitter acid fraction of hops.9 The hops component 8-prenylnaringenin has also exhibited estrogenic activity.8,22 A poorly described paper reported that women started menstruating two days after beginning hops collection; however, hormonal activity was not observed in a variety of hops extracts tested in animal models under controlled conditions.11 Furthermore, hops have shown significant competitive binding to the estrogen receptor alpha (ER alpha) and beta (ER beta) in vitro10 and to intracellular receptors for estradiol (ER) in human breast cancer cell.3 Hops, essential beer ingredients, are a source of prenylflavonoids, including 8-prenylnaringenin (8-PN), one of the most potent phytoestrogens.23
  • Lipid effects: Hops compounds have also been shown to reduce triglycerides and free fatty acid levels.
  • Sedative/hypnotic effects: Mouse models have found hops to have sedative, hypnotic, hypothermic, antinociceptive, and anticonvulsant properties.24 In vivo, the 2-methyl-3-butene-2-ol in the volatile fraction has been identified as a principal sedative-hypnotic constituent of hops.25 In fresh hops, there are only traces of this constituent, but the concentration of 2-methyl-3-butene-2-ol has been shown by other studies to continuously increase after drying, reaching maximum levels (approximately 0.15%) within two years of storing at room temperature. Pharmacologically relevant concentrations of this compound may be acquired in both tea and bath preparations.26 In a clinical trial, quantitative topographical electroencephalography (EEG) detected mild effects on the CNS from a high dosage of a /hops combination product.27 This effect was observed as an increase in delta, decrease in alpha, and a weak decrease in beta power. The valerian/hop extract acts via a central adenosine mechanism, which is possibly the reason for its sleep-inducing and maintaining activity.28 Furthermore, a lozenge containing , extracts from hops, and oat affected the electrical activity in the brain of healthy volunteers. Increases were seen in alpha 1 (relaxed psychophysiological state), alpha 2 (working memory), and beta 1 (anti-anxiety and tranquilizer effect) activity.7

Pharmacodynamics/Kinetics:
  • Animal models have found that a sedative-hypnotic constituent of hops, 2-methyl-3-buten-2-ol, diminishes animal motility by 50% when given intraperitoneally at a dose of 206.5mg/kg.5,6 The onset of activity occurs within two minutes and reaches a maximum response within two hours. The effects of this hop constituent were found to be similar to the sedative drug methylpentynol.

References
  1. Langezaal, C. R., Chandra, A., and Scheffer, J. J. Antimicrobial screening of essential oils and extracts of some Humulus lupulus L. cultivars. Pharm Weekbl Sci 12-11-1992;14(6):353-356. 1475174
  2. Yasukawa, K., Takeuchi, M., and Takido, M. Humulon, a bitter in the hop, inhibits tumor promotion by 12-O- tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Oncology 1995;52(2):156-158. 7854777
  3. Zava, D. T., Dollbaum, C. M., and Blen, M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217(3):369-378. 9492350
  4. Stevens, J. F. and Page, J. E. Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry 2004;65(10):1317-1330. 15231405
  5. Wohlfart, R., Wurm, G., Hansel, R., and Schmidt, H. [Detection of sedative-hypnotic active ingredients in hops. 5. Degradation of bitter acids to 2-methyl-3-buten-2-ol, a hop constituent with sedative-hypnotic activity]. Arch Pharm (Weinheim) 1983;316(2):132-137. 6847343
  6. Wohlfart, R., Hansel, R., and Schmidt, H. [The sedative-hypnotic action of hops. 4. Communication: pharmacology of the hop substance 2-methyl-3-buten-2-ol]. Planta Med 1983;48(2):120-123. 6611749
  7. Dimpfel, W., Pischel, I., and Lehnfeld, R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activity of volunteers. Eur J Med Res 9-29-2004;9(9):423-431. 15546807
  8. Milligan, S. R., Kalita, J. C., Heyerick, A., Rong, H., De Cooman, L., and De Keukeleire, D. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 1999;84(6):2249-2252. 10372741
  9. Zenisek A and Bednar IJ. Contribution of the identification of the estrogen activity of hops. Am Perfumer Arom 1960;75:61.
  10. Liu, J., Burdette, J. E., Xu, H., Gu, C., van Breemen, R. B., Bhat, K. P., Booth, N., Constantinou, A. I., Pezzuto, J. M., Fong, H. H., Farnsworth, N. R., and Bolton, J. L. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem 2001;49(5):2472-2479. 11368622
  11. Fenselau, C. and Talalay, P. Is oestrogenic activity present in hops? Food Cosmet.Toxicol 1973;11(4):597-602. 4758964
  12. Mannering, G. J., Shoeman, J. A., and Shoeman, D. W. Effects of colupulone, a component of hops and brewers yeast, and chromium on glucose tolerance and hepatic cytochrome P450 in nondiabetic and spontaneously diabetic mice. Biochem Biophys Res Commun 5-16-1994;200(3):1455-1462. 8185600
  13. Mannering, G. J. and Shoeman, J. A. Murine cytochrome P4503A is induced by 2-methyl-3-buten-2-ol, 3-methyl- 1-pentyn-3-ol(meparfynol), and tert-amyl alcohol. Xenobiotica 1996;26(5):487-493. 8736060
  14. Swanston-Flatt, S. K., Day, C., Flatt, P. R., Gould, B. J., and Bailey, C. J. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Res 1989;10(2):69-73. 2743711
  15. Simpson, W. J. and Smith, A. R. Factors affecting antibacterial activity of hop compounds and their derivatives. J Appl Bacteriol 1992;72(4):327-334. 1517174
  16. Dixon-Shanies, D. and Shaikh, N. Growth inhibition of human breast cancer cells by herbs and phytoestrogens. Oncol Rep 1999;6(6):1383-1387. 10523716
  17. Henderson, M. C., Miranda, C. L., Stevens, J. F., Deinzer, M. L., and Buhler, D. R. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica 2000;30(3):235-251. 10752639
  18. Mannering, G. J., Shoeman, J. A., and Deloria, L. B. Identification of the antibiotic hops component, colupulone, as an inducer of hepatic cytochrome P-4503A in the mouse. Drug Metab Dispos 1992;20(2):142-147. 1352202
  19. Stevens, J. F., Miranda, C. L., Frei, B., and Buhler, D. R. Inhibition of peroxynitrite-mediated LDL oxidation by prenylated flavonoids: the alpha,beta-unsaturated keto functionality of 2'-hydroxychalcones as a novel antioxidant pharmacophore. Chem Res Toxicol 2003;16(10):1277-1286. 14565769
  20. Miranda, C. L., Yang, Y. H., Henderson, M. C., Stevens, J. F., Santana-Rios, G., Deinzer, M. L., and Buhler, D. R. Prenylflavonoids from hops inhibit the metabolic activation of the carcinogenic heterocyclic amine 2-amino-3-methylimidazo[4, 5- f]quinoline, mediated by cDNA-expressed human CYP1A2. Drug Metab Dispos 2000;28(11):1297-1302. 11038156
  21. Yajima, H., Ikeshima, E., Shiraki, M., Kanaya, T., Fujiwara, D., Odai, H., Tsuboyama-Kasaoka, N., Ezaki, O., Oikawa, S., and Kondo, K. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. J Biol Chem 8-6-2004;279(32):33456-33462. 15178687
  22. Chadwick, L. R., Nikolic, D., Burdette, J. E., Overk, C. R., Bolton, J. L., van Breemen, R. B., Frohlich, R., Fong, H. H., Farnsworth, N. R., and Pauli, G. F. Estrogens and congeners from spent hops (Humulus lupulus). J Nat Prod 2004;67(12):2024-2032. 15620245
  23. Possemiers, S., Bolca, S., Grootaert, C., Heyerick, A., Decroos, K., Dhooge, W., De Keukeleire, D., Rabot, S., Verstraete, W., and Van de, Wiele T. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. J Nutr 2006;136(7):1862-1867. 16772450
  24. Lee KM, Jung JS, Song DK, and et al. Effects of Humulus lupulus extract on the central nervous system in mice. Planta Med 1993;59(Suppl):A691.
  25. Hansel, R., Wohlfart, R., and Coper, H. [Sedative-hypnotic compounds in the exhalation of hops, II]. Z Naturforsch.[C] 1980;35(11-12):1096-1097. 7210807
  26. Hänsel R, Wohlfart R, and Schmidt H. The sedative-hypnotic principle of hops. 3. Communication: contents of 2-methyl-3-butene-2-ol in hops and hop preparations. Planta Med 1982;45:224-228.
  27. Vonderheid-Guth, B., Todorova, A., Brattstrom, A., and Dimpfel, W. Pharmacodynamic effects of valerian and hops extract combination (Ze 91019) on the quantitative-topographical EEG in healthy volunteers. Eur J Med Res 4-19-2000;5(4):139-144. 10799347
  28. Schellenberg, R., Sauer, S., Abourashed, E. A., Koetter, U., and Brattstrom, A. The fixed combination of valerian and hops (Ze91019) acts via a central adenosine mechanism. Planta Med 2004;70(7):594-597. 15254851




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