by Stamatina Mitrou

There is no other plant more connected to beer in people’s mind than hops. However, apart from its long history in beer making process, hops is characterized by numerous medicinal uses as well. Sedative, estrogenic, antimicrobial and potential cytotoxic activity are only a few beneficial effects attributed to hops, and more are yet to come into light through further clinical studies and scientific research. Let’s get to know better the plant that managed to establish a whole new culture in people’s interaction.

Introduction

Hops or Humulus Lupulus is a dioecious perennial climbing vine, member of the Cannabaceae family, located in the in the shrubby part towards the Western end of the Mecklenburgh Square Garden.  Its name, originated from the Latin word ‘‘lupus’’ meaning wolf, indicates the plant’s tendency to climb on other plants, similarly to what the wolf does on sheep. It is found residing mainly in ­­­­the Northern Hemisphere. Reaching a height of up to 8m, it grows during the April to July period, while it is harvested from August until September. The fruits of female hops flowers are dry seeds of poor commercial value. The inflorescences of the female plants form the hop cones, called strobiles, which are the only part of the plant used in the brewing procedure and therefore, are collected before they are allowed to ripen. Strobiles consist of stipular structures, known as bracts and bracteoles, which are attached to a zigzag, hairy axis. As hops starts to ripen, a characteristic fine yellow resinous powder, called lupunin glands, is formed inside the bracteoles and contains all the resins and essential oils which are of vital importance for the brewing process. Apart from its indisputable role in the beer making process, lupunin has also been historically used as a sleep promoting substance. But this is only one among the various medicinal uses of hops throughout the centuries. Let’s discover the worth-mentioning medicinal role of the plant that managed to become part of the everyday life of million people [6], [29].

Popular history and contemporary use

Hops (or hop) has a long tradition in the beer making process, however its potentials are not restricted only to this sector. Interesting medicinal uses and therapeutic actions have been noticed and scientifically confirmed throughout the years, rendering hops a promising plant with multiple aspects. Before focusing on its phytochemical profile and uses as a medicinal plant, it is interesting to review its route throughout the centuries and the way its historical use is strongly connected with its modern utilization.

Regarding its therapeutic uses, hops was first referenced during the ninth century. Before that, it was mainly used for culinary purposes and as major ingredient in bread and beer making [1]. However, from then on, hops gained credibility as a plant used in medical purposes and thus became part of various traditional health techniques, from North American aboriginal medicines to Ayurveda and traditional Chinese medicine. According to [2], the Cherokee used hops as an analgesic, antirheumatic, sedative, gynecological aid for womb and breast problems. Another use they had for hops, was as kidney and urinary aid.Ayurvedic Pharmacopoeia also recognizes hop’s sedative action and recommends it for restlessness associated with nervous tension, indigestion  and headache, as well as an antibacterial agent [3].In traditional Chinese medicine, the ethanol fluid extract dosage form of hops is proposed to treat insomnia, restlessness, dyspepsia, intestinal cramps, and lack of appetite [4].

Hop’s long tradition in the above mentioned traditional-medicine systems, paired with its pharmacological actions confirmed by both in vitro and in vivo animal studies and human clinical trials, support its contemporary medicinal use. Today hops is permitted as a medicinal preparation with sedative properties. In Germany specifically, the use of hops for mood disorders such as anxiety and sleep disturbances, was approved by the Commission E, licensing hops as a standard medicinal tea and an ingredient in about 70 prepared sedative medicines. Similarly, in the United States, infusions and tinctures of hops are used to treat anxiety and unrest [5]. Apart from Germany, in the rest of Europe, the British Herbal Compendium and the European Scientific Cooperative on Phytotherapy (ESCOP) suggest that hops should be used in conditions such as tenseness, restlessness, sleep disorders, excitability and lack of appetite [6], [7].

Phytochemical profile

Hop’s phytochemical profile is synthesized by resinous bitter principles, particularly a-bitter acids (mostly humulone) and b-bitter acids (mostly lupulone) and their oxidative degradation products (2-methyl-3-buten-2-ol), polyphenolic condensed tannins, monoterpenes and sesquiterpenes in the volatile oil (such as b-caryophyllene, farnesene, humulene, b-myrcene), chalcones (mostly xanthohumol), flavonoids (kaempferol, quercetin, isoxanthohumol, 8-prenylnaringenin), phenolic acids and amino acids [5], [6], [7], [8], [9]. Some of these elements exhibit significant pharmacological actions. Humulone, for example, the major a-bitter acid, has been used as an antibiotic and antifungal agent, as well as in beer preserving where its antimicrobial activity has proved important [10]. Additionally, the prenylated flavonoid 8-prenylnaringenin has demonstrated confirmed endocrine properties [11], and flavonoids isoxanthohumol and xanthohumol, have exhibited high chemopreventive, antiproliferative and cytotoxic effects in human cancer cell lines [12], [13].

Pharmacology and Preclinical data

Hops demonstate a vast range of therapeutic actions, some of them confirmed by clinical studies.

• Sedative action

There have been promising animal-based studies that indicate hop’s sedative action, as for example on mice [14] and pigeons [15]. Although the sedative activity is probably attributed to humolone and lupulone, we have yet to distinguish the CNS active constituents of hops and their exact biochemical mechanism [11]. As far as human based studies are concerned, hops has been investigated closely in combination with other notorious sedative herbs. More specifically, there has been a pilot study on patients suffering from nonorganic insomnia and the effects a preparation combination of valerian and hops would have on them. After a two-week treatment, results showcased that some patients demonstrated a decline in both sleep latency and wake time [16], [17]. However, we cannot solely rely on these studies in order to investigate whether hops can act as a sedative on its own, when combined by another sedative, or if it is entirely absent of sedative action [13].

• Estrogenic action

The potential endocrine effects of hops have been extensively investigated throughout the years with the results being promising. The constituent responsible for the estrogenic activity is proved in vitro to be 8-prenylnaringenin [11]. According to some randomized, placebo-controlled, double-blind studies, 8-PN in the form of a standardized hop extract demonstrates the ability to alleviate menopausal symptoms, such as hot flashes and discomfort. Moreover, cell culture models have confirmed 8-PN’s preventing ability of osteoporosis by promoting the differentiation of osteoblasts and inhibiting the activity of osteoclasts [18], [19]. According to these results, we can safely hypothesize that that properly formulated hop preparations can demonstrate beneficial estrogenic properties and find application in modern phytomedicine. During clinical trials, no adverse effects related to the 8-PN application were observed. However, further pharmacokinetic studies would be crucial in order to optimize the dosing regimen [13].

• Antimicrobial action

Hops antimicrobial activity has been tested in vitro by [20]. The results indicated that hop prenylated flavonoids exhibit antistaphylococcal activity. Moreover, the ethyl acetate, acetone, and methanol crude hops extracts, as well as the removal of xanthohumol extracts, can work excellently as natural agents for crop protection against various Fusaria, while methylene chloride extract may be used against Botrytis cinereal [20]. Yet another in vitro study that proves hop’s antimicrobial activity is [21].According to the results of this study, all hop extracts tested showed significant antimicrobial activity against oral streptococci, such as S. mutans, S. sanguis, and S. salivarius. However, definite conclusions cannot be reached unless more in vitro studies are conducted [21], [22].

• Cytotoxic action

During the past 10 years, numerous in vitro studies have been conducted in order to evaluate the potential chemopreventive activity of hop’s components. One of these components, xanthothymol, seems to inhibit in vitro initiation and proliferation of cancer cells, receiving, thus major attention [23] Xanthothymol demonstrates a significant antioxidant activity, which is mainly responsible for its antiproliferative and anticarcinogenic effects [6]. According to [24] xanthothymol significantly decreases the viability of gastric cancer cells by inhibiting their proliferation and inducing apoptosis, but at the same time isn’t toxic for the normal gastric epithelial cell. Moreover, xanthothymol inhibited thyroid cancer cell proliferation and induced their apoptosis. It can therefore be considered as a potential chemotherapeutic candidate for thyroid cancer [25].

Toxicology

There have been no clinical cases confirming toxicity in hops. However, and despite being considered non-toxic, it could cause allergic reactions in people with greater sensitivity. For example, there have been cases where hops-pickers suffered from dermatitis, caused by their allergic reaction to a constituent of fresh hop oil, myrcene [26]. However, no allergies or anaphylaxis from medicinal use of hops have been reported [13].

Efficasy

Hop’s efficacy as a sedative hasn’t yet been confirmed by pharmacodynamic data. Hops has been examined as part of fixed preparations containing other well-known sedative herbs, such as valerian [17]. Although the results of these studies were positive regarding sedative and sleep-promoting activity, we can’t be sure of hop’s exact contribution into this, unless conducting further studies on exclusively hops preparations [13].

Regarding hop’s estrogenic activity, 8-PN-enriched hops extracts for the relief of menopausal symptoms were recently developed and launched as MenoHop® from Biodynamics, Ostend, Belgium. A randomized, double-blind, placebo-controlled study over 12 weeks with 67 menopausal women indicated an important reduction in menopausal discomforts assessed by the Kupperman index and by a simplified patients’ questionnaire in the treatment group after 6 weeks compared to placebo. However, no dose-response relationship could be established, as higher dose appeared less active [6], [27].

In addition, vaginal application of a gel with hops manufactured by Polichem SA, Lugano, Switzerland (Brand names: Gynomunal®, Germany; Esvegyne®, Italy) was tested in an open, non-controlled study with 100 postmenopausal women for 30 days. The results indicated a significant improvement of irritating symptoms such as vaginal dryness, burning, itching, inflammation, dyspareunia and rashes. The study, supported by an additional pilot study by the same group, confirmed a good safety profile for the intended use. However, once more, the study was not designed in a way to separate the effects of hops from those of the other ingredients of the gel (i.e. hyaloronic acid, liposomes, and vitamin E) [28].

Conclusion

Hops (Humulus lupulus) is adioecious perennial climbing vine belonging to the Cannabaceae family, found mainly in the North Hemisphere. Apart from its long tradition in beer making process, hops has been appreciated throughout the centuries for its therapeutic uses as well. Widely used for its sedative, estrogenic, antimicrobial and cytotoxic beneficial effects, hops continues to gain ground into modern phytomedicine as part of many preparations. Although further clinical studies are needed to validate hops multiple actions, its constituents demonstrate significant future potential as effective medicinal agents.

© Stamatina Mitrou. 2019. All rights reserved.

Stamatina Mitrou, MSc Medicinal Natural Products and Phytochemistry 2018-2019 (student). Research Cluster “Biodiversity and Medicines” / Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, Univ. London, 29-39 Brunswick Sq., London WC1N 1AX

Disclaimer

In this essay we do not to advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflets (i.e. for THR products).

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