Mil. Med. Sci. Lett. (Voj. Zdrav. Listy) 2016, vol. 85(1), p. 19-30 ISSN 0372-7025 DOI: 10.31482/mmsl.2016.004 REVIEW ARTICLE HUMULUS LUPULUS L. (HOPS) – A VALUABLE SOURCE OF COMPOUNDS WITH BIOACTIVE EFFECTS FOR FUTURE THERAPIES Jana Olsovska 1, Vanda Bostikova 2 , Martin Dusek 1, Vladimira Jandovska 1,5 , Katerina Bogdanova 4, Pavel Cermak 3, Pavel Bostik 2, Alexandr Mikyska 1, Milan Kolar 4 1 Research Institute of Brewing and Malting, Prague, Czech Republic 2 Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic 3 Department of Clinical Microbiology, Thomayer Hospital, Prague, Czech Republic 4 Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic 5 Faculty of Science, Charles University, Prague, Czech Republic Received 11 th January 2016. Revised 20 th February 2016. Published 4 th March 2016. Summary Hops are a well-known source of resins, essential oils and polyphenolic substances, such as proanthocyanidins or prenylflavonoids with significant representatives of xanthohumol, isoxanthohumol, and 8-prenylnaringenine, and represent an essential ingredient in beer production. Recently, however, many additional bioactive effects of hop compounds have been investigated. A systematic review of the structure-function relationship between the individual hop-derived compounds and their bio-activity has been lacking. In this review we summarize some recent findings in this area from reports from our as well as other studies. It shows multiple bio-medical effects of the individual hop derived compounds, which can act individually, or in a synergistic manner. The hops can serve as a source of bio-active compounds in phyto-medicine and as such, more attention and detailed studies are warranted to utilize the broad spectrum of effects of individual compounds in future treatments. Key words: Humulus lupulus L.; hops; hop resins; hop oils; hop polyphenols; bioactive effects INTRODUCTION bitter and aromatic properties. In addition, hops have been used in cosmetic and pharmaceutical industries, Humulus lupulus L., more precisely flowers especially for their antimicrobial and antiviral effects. (cones) of the female plant represent one of the most The fact, that hops were originally used and added important raw materials for brewing, because of their to beer for its antimicrobial activity as a preservative, classifies this plant as a natural source of compounds with biological effects. University of Defence, Faculty of Military Health Sciences, Department of Epidemiol - An increasing number of pathogenic strains ogy, Trebesska 1575, 500 01 Hradec Kralove, of bacteria (and viruses) resistant to different types Czech Republic of antimicrobials poses a major medical problem. Se - [email protected] condary metabolites of hops have been described Olsovska et al.: Characterization of Bio-Active Compounds in Hops as potent antimicrobial agents against a wide range constipation, sleeping disorders and for purification of microorganisms. The importance of this plant was of blood [7,8]. Records from the 7 th and 9 th (A.D.) supported by the “Medicinal Plant of the Year 2007” centuries show, that the earliest predecessors of hop award granted by the Study Group for the Historical gardens were founded under monastic administra - Development of Medicinal Plant Science at the Uni - tion, where the hops were grown for their medicinal versity of Würzburg, Germany, or by the selection properties together with other herbs [9]. Even at that of hops as the 2008 theme plant by the University time, hop extracts were recognized for their anti-in - of Illinois, Chicago, USA. An increasing number flammatory and anti septic effects as decoctions pre - of scientific publications on the beneficial properties pared from hops were used to treat poorly healing of hops further underscores their importance and is injuries. the main reason for such recognition [1]. Another example of such treatment applications Yellow lupulin glands within hop cones contain is the use of heated hops as a poultice [10] for pneu - resins ( α- acids and β- acids) and essential oils, which monia or treatment of fevers using decoctions from give bitter taste and characteristic aroma to beer. hops [11]. Alcoholic extracts of hops have been also In addition, the matrix of hop cones contains a wide used in Chinese medicine for treatment of pulmonary spectrum of polyphenolic compounds, such as phe - tuberculosis, or acute bacterial dysentery and have nolic acids and proanthocyanidins, or prenylated been also a part of Ayurvedic treatments [12]. Some chalcones, which are generated in the lupulin glands recent studies have shown that alcoholic extracts [2]. The purpose of this review is to summarize bio - from hops possess a strong spasmolytic effect logical activities of all three main groups of hop se - on smooth muscle and thus are effective in conditions condary metabolites (resins, essential oils and characterized by tension of visceral smooth muscles, polyphenols), i.e. functional metabolites formed including nervous colitis, nervous dyspepsia, palpi - in the hop cone during maturation, including their an - tations, nervous or irritable coughs, and ast - tibacterial, antifungal and antiviral activities with hma[13,14]. their future therapeutic potential (Table 1). PHYTOGEOGRAPHY AND BOTANY OF HOPS THE HISTORY OF HOPS Wild hops, which grow in wet areas close to ri - Hops were known as a wild plant already during vers, are widespread on large areas of Europe, Asia the antique times. Historical findings lead to the conc- and North America [15]. lusion that their origin was in Asia, more specifically in the fertile Mesopotamia, the lowlands of Caucasus Today, the production of cultivated common hops and southern Siberia [3]. From the botanical point is concentrated in moist temperate climate areas, with of view, however, the hop plants are thought to have much of the world's production occurring near originated in China, because China is the only the 48 th parallel North. Hop yards are an integral part country in the world where all three species of hops of the countryside around Europe, North and South (H. Lupulus, H. Japanicus, H. Yunnanensis ) are na - Americas, South Africa, Australia and New Zealand. turally found [4-6]. Hops have been grown as a cul - The cultivar plants are grown typically on large flat tivated plant from the beginning of our age. Records areas with acidic soil. Currently the biggest produ - showing hops being used for seasoning and preser - cers of hops include Germany, USA, China and ving of beer by Slavic tribes come from at least 1500 Czech Republic (the production in 2014 was 25 338, to 1000 years BC. Other nations started using hops 38 499, 6 887and 6 202 tons, respectively) [16]. for brewing since the 13 th century (A.D.). Until the 12 th century (A.D.) however, hops were obtained When technological aspects or medical effects of probably only by collecting of wild plants [3]. hops derived products are discussed, it should be noted that these products are derived only from cones Very soon people discovered healing effects of female plants. Humulus lupulus L. is a dioecious of hops, which then found their way into the traditi - twining perennial creeper from Cannabaceae fa - onal medicine. Hops were used, according to an old mily[17], which also includes the genera Cannabis herbarium for medical treatment of various conditi - (hemp) and Celtis (hackberries). The leaves are po - ons, such as leprosy, bad smell of feet, liver diseases, sitioned on the stalk in the opposite manner on 7 20 Olsovska et al.: Characterization of Bio-Active Compounds in Hops Table 1. List of antibacterial, antifungal and antiviral activities of hop compounds Hop compounds Microorganism tested activity +/- Reference No. RESINS (soft) + 38 Candida albicans + 38 Trichophyton mentagrophytes var. interdigidale + 38 Fusarium + 38 Mucor + 38 Lactobacillus spp + 39-42 Pediococcus spp + 39-42 Streptococcus mutans + 39-42 Streptococcus sanguis + 39-42 Streptococcus salivarius + 39-42 Clostridium perfringens + 39-42 Staphylococcus aureus + 39-42 Micrococcus + 39-42 Clostridium difficile + 39-42 Clostridium botulinum + 39-42 Helicobacter pylori + 39-42 Bacillus subtilis + 39-42 Listeria monocytes + 43, 44 Mycobacterium tuberculosis + 45 OILS Bacillus subtilis + 44 Staphylococcus aureus + 44 Trichophyton mentagrophytes var. interdigitale + 44 Escherichia coli - 44 Candida albicans - 44 POLYPHENOLS Staphylococcus aureus + 38 Streptococcus mutans + 40 bovine viral diarrhea virus (BVDV) + 42 surrogate model of hepatitis C virus (HCV) 42 human immunodeficiency virus (HIV) - 42 influenza A virus (FLU-A) - 42 influenza B virus (FLU-B) - 42 rhinovirus (Rhino) + 42 respiratory syncytial virus (RSV) - 42 yellow fever virus (YFV) - 42 cytomegalovirus (CMV) + 42 hepatitis B virus (HBV) + 42 herpes simplex virus type 1 (HSV-1) + 42 herpes simplex virus type 2 (HSV-2) + 42 21 Olsovska et al.: Characterization of Bio-Active Compounds in Hops to 12 cm long leafstalks and are heart-shaped with dreds of varieties of hops, which differ substantially coarsely toothed edges. The female flowers (often in the content and chemical profile of hop oils and called cones) consist of short green spikelets (called bitter acids (and related polyphenols) [5, 22]. Based hop cones, seed cones or strobiles) and secrete a fine on genetic markers, hop varieties can be divided into yellow resinous powder from structures called four groups: hops of the European origin of the Saaz lupulin glands. Lupulin glands synthesize the resins group, hops of the European origin of the Fuggle and essential oil [18, 19], which give the characteristic group, hops of the American origin and hops of mixed bitter taste and aroma to beers, but also stabilize origin [23] (Figure 1) New hop varieties are bred by the foam and final product [20]. Special vacuoles crossing of a different genetic material to achieve of the external system of lupulin glands represent rich desired characteristics, such as high yield, disease reservoirs of brewing and pharmacologically impor- resistance and content and composition of resins and tant substances, which are often called secondary oils.