Humulus lupulus L.

Last updated: 14 Apr 2017

Scientific Name

Humulus lupulus L.

Synonyms

Humulus cordifolius Miq., Humulus lupulus var. cordifolius (Miq.) Maxim. ex Franch. & Sav., Humulus lupulus var. lupulus, Humulus volubilis Salisb. [Illegitimate], Humulus vulgaris Gilib., Lupulus amarus Gilib., Lupulus communis Gaertn., Lupulus humulus Mill., Lupulus scandens Lam. [Illegitimate]. [1]

Vernacular Name

English European hop, hop, hops, [2] common hop, bine [3]
China Pi jiu hua [2][4]
North America Common hop(s), hop(s), houblon, lupulo [2].

Geographical Distributions

Humulus lupulus is originated from Gansu, North Sichuan, Xinjiang, North Africa, North and North East Asia, Europe, and East North America. [4]

Botanical Description

H. lupulus is a perennial plant that belongs to Cannabaceae family. [4]

The petiole is usually shorter than leaf blade; leaf blade 3-5(-7)-lobed, sometimes simple, 4-11 × 4-8 cm, abaxially glabrous or with scattered soft pubescence but without rigid spinulose hairs on veins, adaxially with few or no cystolith hairs marginally when young, base cordate, margin coarsely serrate, apex acute. [4]

Female flowers 2 per bract at least in middle of inflorescence; bracts imbricate into a globose spike. Infructescences are globose, 3-4 cm in diameter; bracts ovoid, 1.5-2 cm, dry, membranous, apex acute. Achenes are flat and included in bracts. [4]

Cultivation

H. lupulus is cultivated throughout China, especially in East Shandong (Qingdao) and Xinjiang. [4]

Chemical Constituent

Female inflorescences of H. lupulus was found to contain xanthohumol compounds (e.g. 5"-isopropyl-5"-hydroxydihydrofurano[2",3":3',4']-2',4-dihydroxy-6'-methoxychalcone; 5"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":3',4']-2',4-dihydroxy-6'-methoxychalcone; and dehydrocycloxanthohumol). [5]

H. lupulus was found to contain essential oil, humulones, and lupulones. [6]

H. lupulus was found to contain humulone, lupulone, cohumulone, colupulone, adhumulone, and adlupulone. [7]

H. lupulus was found to contain alpha-acids, beta-acids, prenylated chalcones, desmethylxanthohumol, and xanthohumol. [8]

Plant Part Used

Strobiles. [9]

Traditional Use

H. lupulus has been used since the Roman times in brewing beer and other alcoholic beverages and as a traditional gastrointestinal, nerve, and sedative tonic. H. lupulus is stated to possess sedative, hypnotic, antispasmodic, and topical bactericidal properties [10]. Traditional uses of H. lupulus include neuralgia, insomnia, excitability, topically for skin ulcerations, and primarily for restlessness associated with nervous tension [11].

Preclinical Data

Pharmacology

Antimicrobial activity

Lupulone, humulone, isohumulone, and humulinic acid are active constituents isolated from H. lupulus extract that exhibited antibacterial properties in laboratory animals, specifically against Gram-positive bacteria. These constituents caused membrane leakage in Bacillus subtilis 168. [12]

Chloroform extract of H. lupulus cones was found to exhibit antibacterial activity against the Gram-positive bacteria (Bacillus subtilis andStaphylococcus aureus) and the fungus (Trichophyton mentagrophytes var.interdigitale), but almost no activity against the Gram-negative bacterium (Escherichia coli) and the yeast (Candida albicans) used in the screening. [13]

Trans-isohumulone isolated from H. lupulus was found to exhibit a greater antibacterial activity against Lactobacillus brevis compare to humulone, colupulone, and trans-humulinic acid. [14]

In vitro studies showed synergistic effects of H. lupulus constituents and several antibiotics in inhibiting Gram-positive bacteria and enhancing the inhibition of the antibiotics on Gram-negative bacteria. [15]

Antiviral activity

Xanthohumol, isoxanthohumol, and iso-alpha acids isolated from H. lupulus were found to have low to moderate antiviral activity against several types of viruses. [16]

Xanthohumol isolated from H. lupulus was found to inhibit the HIV-1 reverse transcriptase, [17] the viral cytopathic effects and production of HIV-1 p24 antigen in C8166 lymphocytes. In addition to this, it was also shown to have inhibitory effect on the viral replication in peripheral blood mononuclear cells [18].

Xanthohumol showed strong anti-BVDV (Bovine viral diarrheal virus, a surrogate for Hepatitis C virus) effect in a cell culture system. Apart from inhibition of the viral cytopathic effects, it inhibited BVDV E2 protein expression and reduced the viral RNA levels in a dose-dependent manner. When compared with drugs used for the treatment of chronic hepatitis C, xanthohumol’s antiviral effect was superior to ribavirin but weaker than alpha-interferon (IFN) [19]. Interestingly, the combination of xanthohumol and IFN exhibited stronger antiviral activity [20].

Sedative activity

CO2 extract of H. lupulus and its fraction containing alpha-acids was tested on the central nervous system of rats. Both tested substances were able to prolong pentobarbital sleeping time, without affecting the latency to the loss of the righting reflex. This effect was dose-dependent, starting from a minimal dose of 10 mg/kg. [21]

Sedative action of H. lupulus has been shown in many laboratory studies. H. lupulus has been reported to increase narcotic-induced sleeping time [22][23] and improve sleep disturbances when given in combination with other sedative herbs [11].

In vitro study reported that the H. lupulus component of Ze 91019 interact with serotonin and melatonin receptor subtypes which could explain its sedative effect. [24]

Estrogenic activity

The female flowers of H. lupulus have been reported to have a mild estrogenic activity, attributed to the presence of 8-prenylnaringenin (PN), isoxanthohumol, 6-PN and geranylated flavonoids. In in vitro study, 8-PN was reported to bind to both α- and β-estrogen receptors (ER) with higher affinity for the ER-alpha receptors [25]. 8-PN also has been regarded as an oestrogen agonist in female reproductive organs. It induced mitotic activity in the vaginal epithelium [26] and increased uterine weight of ovariectomised rats [27].

Anticancer activity

A few in vitro studies have been reported that flavonoid constituents found in H. lupulus (including xanthohumol, dehydrocycloxanthohumol and isoxanthohumol) had antiproliferative activity (dose dependent) in certain human breast cancer, [28][29] thyroid cancer, [30] and prostate cancer [31].

Flavanoid compounds isolated from H. lupulus was found to exhibit antiproliferative effect on various cancer cell lines may be due, in part, to inhibition of cytochrome P450 enzymes (including CYP1A1, CYP1B1 and CYP1A2) that activate carcinogens. [32]

Xanthohumol, isoxanthohumol [33] and 8-prenylnaringenin [34] isolated from H. lupulus were found to exhibit anticancer activity in human breast cancer cell lines by reduction of oestrogen formation (by inhibiting aromatase), cell proliferation and induce apoptosis.

In addition, xanthohumol isolated from H. lupulus has been shown in many in vitro studies to exert anticarcinogenic effects at different stages of carcinogenesis. It induced quinone reductase, an enzyme involved in detoxification of reactive metabolites, [35] protected DNA damage against procarcinogens, [36] act as an antioxidant and anti-inflammatory agent and a free radical scavenger [37][38].

Xanthohumol [39] and 8-prenylnaringenin [40] isolated from H. lupulus also inhibited induced angiogenesis by suppressing endothelial cell invasion, migration and proliferation.

In another study on human colon cancer cell lines, proanthocyanidins isolated from H. lupulus were reported to exert cytotoxic effect by increasing the levels of intracellular reactive oxygen species, protein carbonyls and cytoskeletal disruption. [41]

Antiobesity activity

In vivo studies reported that isohumolones isolated from H. lupulus were able to reduce body weight and plasma triglycerol levels. It was shown that isohumolones modulated lipid metabolism via activation of peroxisome proliferator-activated receptors (PPARs). [42][43][44][45]

Gastroprotective activity

The stimulating effects of H. lupulus on gastric secretion have been reported in laboratory animals [46][47]. H. lupulus reportedly exerts a strong spasmolytic action on smooth muscles when used as an extract [48].

Anaphrodisiac activity

An in vivo study reported that 8-prenylnaringenin isolated from H. lupulus exerted a dose-dependent anaphrodisiac effect on naïve male rats. [49]

Toxicity

No documentation.

Clinical Data

Clinical findings

Sedative activity

Human studies of the sedative action generally refer to H. lupulus being used in combinations with other sedative herbs. The efficacy of Valerian-H. lupulus combination (Ze 91019) in treating insomnia was shown in several studies. [50][51]

Estrogenic activity

Human studies evaluating the benefit of H. lupulus in treating menopausal symptoms showed that 100 micrograms of 8-prenylnaringenin daily for 12-16 weeks able to improve menopausal discomforts. [52][53]

Antiobesity activity

The weight reduction effect of isohumolones isolated from H. lupulus was further tested in human and showed that 48 mg isohumolones per day for 12 weeks significantly decreased body weight of prediabetic patients. [54]

Antidiabetic activity

Isohumolones were also reported to have anti-hypertensive and anti-glycaemic effects in human studies. [54]

Precautions

Based on evidence that constituents contained in H. lupulus strobiles have estrogenic activity, use with caution in individuals susceptible to hormonally related cancers, such as breast, ovarian and prostate. [24]

Side effects

No documentation.

Pregnancy/Breast Feeding

No documentation.

Age limitation

No documentation.

Adverse reaction

No documentation.

Interaction & Depletion

Interaction with drug

A laboratory study reported that H. lupulus may affect the way certain medications are broken down in the body. This may alter the effects of these medications and possibly the dose(s) needed for treatment. Use with caution. [32]

Studies report that H. lupulus may cause sedation, which may enhance the effects of alcoholic beverages. These drugs include beer, wine, hard liquor, and mixed drinks. Use with caution. [55]

Studies report that H. lupulus may cause sedation, which may enhance the effects of these medications and possibly the dose needed for treatment. These drugs include alprazolam, diazepam, lorazepam, clorazepate dipotassium, chlordiazepoxide, oxazepam, buspirone, butabarbital, diphenhydramine, doxepin, hydroxyzine, meprobamate, amitriptyline, amobarbital, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, trimipramine, maprotiline, mirtazapine, trazodone, bupropion, venlafaxine, nefazodone, citalopram, fluoxetine, fluvoxamine, paroxetine, phenobarbital, pentobarbital, mephobarbital, secobarbital, thiopental, methohexital, sertraline, phenelzine, tranylcypromine, norethindrone, ethynodiol diacetate, norgestrel, norgestimate, ethinyl estradiol, drospirenone, desogestrel, levonorgestrel, conjugated estrogens, estradiol, estrone, esterified estrogens, estropipate, ethinyl estradiol, raloxifene, transdermal estradiol, vaginal estrogens, and isocarboxazid. Use with caution. [22][25][55][56][57]

Interaction with other Herbs

No documentation.

Contraindications

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

No documentation.

References

  1. The Plant List. Ver1.1. Humulus lupulus L. [homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2017 Apr 14]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2855039.
  2. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume III E-L. Boca Raton, Florida: CRC Press, 2012; p. 507.
  3. Herbal Medicine Research Centre, Institute for Medical Research. Compendium of medicinal plants used in Malaysia. Volume 2. Kuala Lumpur: HMRC IMR, 2002; p. 23.
  4. Flora of China. Humulus lupulus Linnaeus. [homepage on the internet]. No date [cited 2017 Apr 14]. Available from: http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200006377.
  5. Yilmazer M, Stevens JF, Deinzer ML, Buhler DR. In vitro biotransformation of xanthohumol, a flavanoid from hops (Humulus lupulus), by rat liver microsomes. Drug Metab Dispos. 2001;29(3):223-231.
  6. Verschuere M, Sandra P, David F. Fractionation by SFE and microcolumn analysis of the essential oil and the bitter principles of hops. J Chromatogr Sci. 1992;30(10):388-391.
  7. Verzele M, Potter MDE. High-performance liquid chromatography of hop bitter substances. J Chromatogr. 1978;166:320–326.
  8. De Keukeleire J, Ooms G, Heyerick A, Roldan-Ruiz I, Van Bockstaele E, De Keukeleire D. Formation and accumulation of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol during flowering of hops (Humulus lupulus L.). J Agric Food Chem. 2003;51(15):4436-4441.
  9. Koetter U, Biendl M. Hops (Humulus lupulus): A review of its historic and medicinal uses. HerbalGram. 2010;(87):44-57.
  10. Newall CA, et al. Herbal medicines: A guide for health care professionals. London: The Pharmaceutical Press, 1996; p. 162-163.
  11. Bradley PR, editor. British herbal compendium volume 1. Bournemouth: British Herbal Medicine Association, 1992; p. 128-129.
  12. Teuber M, Schmalreck AF. Membrane leakage in Bacillus subtilis 168 induced by the hop constituents lupulone, humulone, isohumulone, and humulinic acid. Arch Mikrobiol. 1973;94(2):159-171.
  13. Langezaal CR, Chandra A, Scheffer JJC. Antimicrobial screening of essential oils and extracts of some L. cultivar. Pharm Weekbl Sci. 1992;14(6):353-356.
  14. Simpson WJ, Smith AR. Factors affecting antibacterial activity of hop compounds and their derivatives. J Appl Bacteriol. 1992;72(4):327-334.
  15. Natarajan P, Katta S, Andrei I, Babu Rao Ambati V, Leonida M, Haas GJ. Positive antibacterial co-action between hop (Humulus lupulus) constituents and selected antibiotics. Phytomedicine. 2008;15(3):194-201.
  16. Buckwold VE, Wilson RJ, Nalca A, et al. Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res. 2004;61(1):57-62.
  17. Matthée G, Wright AD, König GM. HIV reverse tarsncriptase inhibitors of natural origin. Planta Med. 1999;65(6):493-506.
  18. Wang Q, Ding ZH, Liu JK, Zheng YT. Xanthohumol, a novel anti-HIV-1 agent purified from Hops Humulus lupulus. Antiviral Res. 2004;64(3):189-194.
  19. Zhang N, Liu Z, Han Q, et al. 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. 2009;38(4):332-340.
  20. Zhang N, Liu Z, Han Q, Chen J, Lv Y. Xanthohumol enhances antiviral effect of interferon alpha-2b against bovine viral diarrhea virus, a surrogate of hepatitis C virus. Phytomedicine, 2010;17(5):310-316.
  21. Zanoii P, Rivasi M, Zavatti M, Brusiani F, Baraldi M. New insight in the neuropharmacological activity of Humulus lupulus L. J Ethnopharmacol. 2005;102(1):102-106.
  22. Lee KM, Jung JS, Song DK, Kraeuter M, Kim YH. Effects of Humulus lupulus extract on the central nervous system in mice. Planta Med. 1993;59(Suppl):A691.
  23. Schiller H, Forster A, Vonhoff C, Hegger M, Biller A, Winterhoff H. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. 2006;13(8):535-541.
  24. Abourashed EA, Koetter U, Brattström A. In vitro binding experiments with a Valerian, hops and their fived combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. 2004;11(7-8):633-638.
  25. Miligan SR, Kalita JC, Pocock V, et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavanoids. J Clin Endocrinol Metab. 2000;85(12):4912-4915.
  26. Miligan S, Kalita J, Pocock V, et al. Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin. Reproduction. 2002;123(2):235-242.
  27. Overk CR, Guo J, Chadwick LR, et al. In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin. Chem Biol Interact. 2008;176(1):30-39.
  28. Miranda CL, Stevens JF, Helmich A, et al. Antiproliferative and cytotoxic effects of prenylated favanoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem Toxicol. 1999;37(4):271-285.
  29. Gerhauser C, Alt A, Heiss E, et al. Cancer chemoprotective activity of xanthohumol, a natural product derived from hop.
  30. Cook MR, Luo J, Ndiaye M, Chen H, Kunnimalaiyan M. Xanthohumol inhibits the neuroendocrine tracscription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer. Am J Surg. 2010;199(3):315-318.
  31. Delmulle L, Bellahcène A, Dhooge W, et al. Anti-proliferative properties of prenylated flavanoids from hops (Humulus lupulus L.) in human prostate cancer cell lines. Phytomedicine. 2006;13(9-10):732-734.
  32. Henderson MC, Miranda CL, Steven JF, Deinzer ML, Buhler DR. In vitro inhibition of human P450 enzymes by prenylated flavanoids from hops, Humulus lupulus. Xenobiotica. 2000;30(3):235-251.
  33. Monteiro R, faria A, Azevedo I,m Calhau C. Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavanoids. J Steroid Biochem Mol Biol. 2007;105(1-5):124-130.
  34. Brunelli E, Minassi A, Appendino G, Moro L. 8-prenylnaringenin, inhibits estrogen receptor-alpha mediated cell growth and induces apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2007;107(3-5):140-148.
  35. Dietz BM, Kang YH, Liu G, et al. Xanthohumol isolated from Humulus lupulus inhibits menadione-induced DNA damage through induction of quinine reductase. Chem Res Toxicol. 2005;18(8):1295-1305.
  36. Plazar J, Filipic M, Groothuis GMM. Antigenotoxic effect of xanthohumol in rat liver slices. Toxicol In Vitro. 2008;22(2):318-327.
  37. Vogel S, Barbic M, Jürgenliemk G, Heilmann J. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. Eur J Med Chem. 2010;45(6):2206-2213.
  38. Kac J, Plazar J, Mlinaric A, Zaqura B, Lah TT, Filipic M. Antimutagenicity of hops (Humulus lupulus L.): Bioassay-directed fractionation and isolation of xanthohumol. Phytomedicine. 2008;15(3):216-220.
  39. Albini A, Dell’Eva R, Vené R, et al. Mechanisms of the antiangiogenic activity by the hop flavanoid xanthohumol: NF-kappaB and Akt as targets. FASEB J. 2006;20(3):527-529.
  40. Pepper MS, Hazel SJ, Hümpel M, Schleuning WD. 8-prenylnaringenin, a novel phytoestrogen, inhibits angiogenesis in vitro and in vivo. J Cell Physiol. 2004;199(1):98-107.
  41. Chung WG, Miranda CL, Stevens JF, Maier CS. Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species. Food Chem Toxicol. 2009;47(4):827-836.
  42. Shimura M, Hasumi A, Minato T, et al. Isohumulones modulate blood lipid status through the activation of PPAR alpha. Biochim Biophys Acta. 2005;1736(1):51-60.
  43. Miura Y, Hosono M, Oyamada C, Odai H, Oikawa S, Kondo K. Dietary isohumulones, the bitter components of beer, raise plasma HDL-cholesterol levels and reduce liver cholesterol and triaclygltcerol contents similar to PPARalpha activations in C57BL/6 mice. Br J Nutr. 2005;93(4):559-567.
  44. Yajima H, Noguchi T, Ikeshima E, et al. Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents. Int J Obes (Lond). 2005;29(8):991-997.
  45. Yajima H, Ikeshima E, Shiraki M, et al. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. J Biol Chem. 2004;279(32):33456-33462.
  46. Krivenko VV, Potebnia GP, Loïko VV. [Experience in treating digestive organ diseases with medicinal plants]. Vrach Delo. 1989;(3):76-78.
  47. Kurasawa T, Chikaraishi Y, Naito A, Toyoda Y, Notsu Y. Effect of Humulus lupulus on gastric secretion in arat pylorus-ligated model. Biol Pharm Bull. 2005;28(2):353-357.
  48. Caujolle F, Pham-Huu-Chanh, Duch-Kan P, Bravo-Diaz L. [Spasmolytic action of hop (Humulus lupulus, Cannabinacees)]. Agressologie. 1969;10(5):405-410.
  49. Zanoli P, Zavatti M, Rivasi M, Benelli A, Avallone R, Baraldi M. Experimental evidence of the anaphrodisiac activity of Humulus lupulus L. in naive male rats. J Ethnopharmacol. 2009;125(1):36-40.
  50. Morin CM, Koetter U, Bastien C, Ware JC, Wooten V. Valerian-hops combination and diphenhydramine for treating insomnia: A randomized placebo-controlled clinical trial. Sleep. 2005;28(11):1465-1471.
  51. Koetter U, Schrader E, Käufeler R, Brattström A. 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. 2007;21(9):847-851.
  52. Hayerick A, Varvarcke S, Depypere H, Bracke M, De Keukeleire D. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas. 2006;54(2):164-175.
  53. Erkkola R, Vervarcke S, Vansteelandt S, Rompotti P, De Keukeleire D, Heyerick A. A randomized, double-blind, placebo-controlled, cross-over pilot study on the use of standardized hop extract to alleviate menopausal discomforts. Phytomedicine. 2010;17(6):389-396.
  54. Obara K, Mizutani M, Hitomi Y, Yajima H, Kondo K. Isohumulones, the bitter component of beer, improve hyperglycemia and decrease body fat in Japanese subjects with prediabetes. Clin Nutr. 2009;28(3):278-284.
  55. Wohlfart R, Wurm G, Hänsel R, 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.
  56. Hänsel R, Wohlfart R, Coper H. [Sedative-hypnotic compounds in the exhalation of hops, II]. Z Naturforsch C. 1980;35(11-12):1096-1097.