HighlightsHops are ubiquitous in modern and ancient cul-ture, with recent research pointing towards efficacyin treatment of mild insomnia[2, 4, 6, 7].Hops are thought to work by modulating theGABAAreceptors[1].BackgroundHumulus lupulusL., known as Hops, is a memberof the Cannabaceae family and is perennial climbingplant which produces female inflorescences containingtrichomes, which are production sites for many sec-ondary metabolites[2]. Hops have always been of eco-nomic and societal interest mainly due to its usage inbeer production, however, recent research has also re-newed interest in the volatile oils of hops for therapeuticuses[2, 4, 7].Three classes of secondary metabolites are mostprominent in hops – bitter acids, hop essential oils, andpolyphenols[4]. These compounds have been found tohave pharmacological properties ranging from sedativeactivities to estrogenic and chemopreventive activities[2,4, 7].The main essential oils present in hops ared-Limonene,β-Myrcene,β-Ocimene,α-Pinene, Terpino-lene, Geraniol, and Linalool[2]. Sesquiterpenes includeBergamotene, Bisavolene,β-Caryophyllene, and Humu-lene, among many others[2]. Other compounds presentin hops which are known to have biological activity include Humulone and Lupulone[2], as well as isoxantho-humol (IXN) and 6-prenylnaringenin (6PN)[1]. All ofthe biologically active compounds in hops compromiseabout 30% by weight of the cones[4].In animals, hops have been found to produce seda-tive and hypnotic effects, however in humans, the lupulinand bitter acid compounds from hops do not so clearlyproduce these effects[6]. Some studies which examinedthe effects of the combination of valerian and hops indi-cate that there were some improvements in certain sleepparameters[5, 6], although more research is warranted.Hop research in the last few decades has been largelydedicated to the biological activities of single hop compo-nentsin-vitroin animal models[7], rather than in clinical trials with humans.Mode of ActionAlthough not much is known about the exact mecha-nisms in which hop components yield sedative effects,recent research has elucidated that one of the mainmodes of action could be through modulation of GABAAreceptors[1].It was found, electrophysiologically in mice, that hu-mulone is a positive allosteric modulator of GABAAreceptors[1]. Humulone was also found to inhibitcyclooxygenase-2 (COX-2) expression via interactionwith NFkappaB[4].It was also found that this specific modulation by hu-mulone caused sedative and hypnotic effects in mice[1].Additionally, it was found that additional hop flavanoidssuch as isoxanthohumol (IXN) and 6-prenylnaringenin(6PN) may also potentiate humulone’s effects via addi-tive mechanisms on the GABAAreceptors[1].Other prenylated polyphenols and derivatives with aphloroglucinol common substrate also exhibit interestingbiological activities, such as potential inhibition mecha-nisms on the conversion of procarcinogens to carcinogensand radical oxygen species scavenging[4].Pharmacological EffectsHops have been found to produce sedative and hypnoticeffects in animals, although lupulin and bitter acids didnot cause sleep-inducing effects in humans – however inhumans, valerian in combination with hops was associ-ated with improvements in sleep latency and quality ofsleep[4, 6]. However, not all studies point to improvements in sleep quality in humans, even in combinationwith other compounds[3].The Committee on Herbal Medicinal Products of theEuropean Medicines Agency (EMEA) report the tradi-tional use of hops for the relief of mild symptoms of men-tal stress and insomnia[7].As described previously, it is thought that the sleep-inducing effects of hops are related to modulation of theGABAAreceptors[1], although it is thought that someof the other pharmacological effects seen are also po-tentially due to interactions of the hop compounds withmelatonin and serotonin receptors[2].Other pharmacological effects of hops include its pro-estrogenic properties due to its flavanone compounds[2,7]. It was seen in somein-vivostudies that standard-ized hop extract was effective in managing menopausalsymptoms with a protective effect on bone loss[2].The bitter acids in hops also contribute to someantimicrobial activities, including the prevention ofbiofilms[2, 7].Lastly, some hop phenolic compounds such as xan-thohumol are considered cancer-preventive agents andare able to inhibit the progression and initiation of dif-ferent stages of carcinogenesisin-vitro[2, 7]. Addition-ally, oxidative stress and markers of cardiovascular riskand inflammation were also decreased in a fairly limitedstudy[6].Hops are considered largely safe, with the largest po-tential issue being allergies to the plant itself[7] or largedoses of isolated compounds (such as humulone, whichwould not be present in sufficient quantities in the plantto be harmful)[2].Potential UsesAs discussed above, the traditional use and use sup-ported by literature and various European Healthagencies[7] is for the usage of hops in mild insomnia[4, 6],especially in combination with Valerian root[3].References[1] A. Benkherouf, K. Eerola, S. Soini, and M. Uusi-Oukari. Humulone modulation of gabaa receptorsand its role in hops sleep-promoting activity.Fron-tiers in Neuroscience, 14:1100, 2020.[2] L. Bocquet, S. Sahpaz, J. L. Hilbert, C. Rambaud,and C. Rivière. Humulus lupulus l., a very popularbeer ingredient and medicinal plant: overview of itsphytochemistry, its bioactivity, and its biotechnology.17(5):1047–1090, 2018.3] C. Cornu, L. Remontet, N. Florence, A. Nico-las, N. Feugier-Favier, P. Roy, B. Claustrat,M. Saadatian-Elahi, and B. Kassaï. A dietary supple-ment to improve the quality of sleep: a randomizedplacebo controlled trial. 10(1), 2010.[4] D. De Keukeleire and A. Heyerick. Prenylflavonoidsaccount for intriguing biological activities of hops.ActaHortic., 668:175–190, 2005.[5] S. Salter and S. Brownie.Australian Family Physi-cian, 39(6):433–437, 2010.[6] C. Ulbricht, E. Basch, S. Basch, W. Chao, J. Con-quer, D. Costa, S. Culwell, C. Dacey, J. Guilford,P. Hammerness, E. Higdon, R. Isaac, M. Lynch,C. Orlando, E. Rusie, M. Varghese, M. Vora,R. Windsor, and J. Woods. Hops (humulus lupulus):An evidence-based systematic review by the natu-ral standard research collaboration.Alternative andComplementary Therapies, 18(2):98–108, 2012.[7] P. Zanoli and M. Zavatti. Pharmacognostic and phar-macological profile of humulus lupulus l.Journal ofEthnopharmacology, 116(3):383–396, 2008.This document was created on November 11, 2021 and last up-dated on November 14, 2021.
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