Review Cite This: J. Agric. Food Chem. XXXX, XXX, XXX−XXX
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Role of Characteristic Components of Humulus lupulus in Promoting Human Health Mengfei Lin,†,‡,∥ Diying Xiang,§,∥ Xiaoyang Chen,*,†,‡ and Heqiang Huo*,∥ †
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State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, South China Agricultural University, Guangzhou 510642, China ‡ Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, Guangzhou 510642, China § College of Horticulture, Hebei Agricultural University, Hebei 071066, China ∥ Mid-Florida Research & Education Center, IFAS, University of Florida, Apopka, Florida 32703, United States ABSTRACT: Over the next 50 years, the prevention and control of chronic diseases, such as obesity, cardiovascular disease, Alzheimer’s disease, and many cancers, will be one of the most critical challenges in human health. Plant biochemistry and phytonutrient supplements are a promising complementary therapy for the management of chronic disease. Among them, Humulus lupulus has attracted special attention throughout the world because it contains numerous dietary phytochemicals that not only contribute to the aroma and flavor of beer but may also be used for medicinal purposes, as its properties include antiseptic, (an)aphrodisiac, anticancer, antiplatelet, antibacterial, antidiuretic, anti-inflammatory, sedative, hypnotic, and stomachic properties. This review sought to identify and understand the risk factors for chronic disease with a focus on two types of phytochemicals, bitter acids and xanthohumol. The goal was to understand how their metabolites promote human health and reduce the risk of chronic disease. KEYWORDS: Humulus lupulus, chronic diseases, cancer, bitter acids, xanthohumol
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INTRODUCTION Cancer is one of the major causes of death worldwide. It is not caused by infectious agents but, rather, by an unhealthy diet, excessive alcohol consumption, tobacco use, genetic and environmental factors, and decreased physical activity.1 Cancer is a complex disease with several genome instability-related cellular causes, such as the limitless potential for replication, evasion of apoptosis, and tissue metastasis.2 Many other chronic or noncommunicable diseases aside from cancer, including diabetes, stroke, Alzheimer’s disease, and cardiovascular disease, are major threats to human health and will continue to be so over the next 50 years.3 To lower the increasing probability of chronic disease in the world’s population, the continued development of improved and novel chemotherapeutic agents is required. Synthetic agents, unlike natural extracts from vegetables or fruits, may cause immune system weakness and body metabolic disorders. Over the past 30 years, an increasing number of researchers have focused on plant-based foods and products, which have been abundant sources of anticancer agents, possessing a variety of chemical structures and biological activities.4 Epidemiological and clinical studies have increasingly focused on beer, because the health-promoting components of this alcoholic beverage can significantly reduce the global socioeconomic burden imposed by cardiovascular disease and cancer, and aid in the understanding of the pathways of these diseases. For example, at moderate levels, beer may protect against venous thrombosis.5 A diverse range of healthpromoting components are present in beer, including amino acids, vitamins, carbohydrates, bitter acids, and various flavonoid compounds; these plant secondary metabolites © XXXX American Chemical Society
have health-promoting effects and may, thus, reduce the burden of chronic disease. One of the most important raw materials used in beer production is hops (Humulus lupulus L.), which serve as a primary dietary source of bitter acids and xanthohumol. At present, most of the H. lupulus crop is cultivated for brewing purposes, with the remainder primarily used to produce phytomedicines and botanical dietary supplements; the cultivation occurs in many countries located between latitudes 35° and 55° of the Southern and Northern Hemispheres, especially in Europe, Germany, and the USA.6,7 Historical evidence suggests that H. lupulus was primarily used for medicinal purposes rather than for beer brewing before the eighth century AD, and its cone-shaped infructescences were first added during brewing as a flavoring agent and natural antiseptic during the Middle Ages.8 In modern herbal medicine, hops or hop cones, the female inflorescences of Humulus, are well-known throughout the world not only because they contribute to the aroma and flavor of beer but also because of their medicinal uses, as their properties include antiseptic, (an)aphrodisiac, antidiuretic, anti-inflammatory, sedative, hypnotic, and stomachic properties.9,10 For example, H. lupulus extracted using supercritical CO2 possesses antiplatelet activity that not only significantly reduces ADPinduced platelet aggregation but also ameliorates the anticoagulant activity of the human endothelium; this suggests that H. lupulus may prevent cardiovascular diseases, which are Received: Revised: Accepted: Published: A
June 17, 2019 July 6, 2019 July 9, 2019 July 9, 2019 DOI: 10.1021/acs.jafc.9b03780 J. Agric. Food Chem. XXXX, XXX, XXX−XXX
Review
Journal of Agricultural and Food Chemistry Table 2. Different Varieties of Hops6
the number one cause of death globally, representing 17.9 million deaths in 2016.11,12
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variety
CHARACTERISTICS OF H. lupulus AND DRY-HOPPING TECHNIQUES Humulus lupulus (2n = 18 + XY/XX) is a climbing perennial plant that generally produces male and female flowers on separate plants. However, some H. lupulus plants exhibit pseudomonoecious flowering, without viable pollen.13 Female plants produce 2.5−5 cm long cone-like inflorescences, also known as hops which are composed of overlapping membranous bracts, whereas male plants produce multibranched panicles comprising many tiny flowers (7.5−12.5 cm long).14 Hops contain lupulin glands, which produce groups of compounds that are economically valuable to the beer-brewing industry and as health products. Males produce small quantities of lupulin glands in both flowers and leaves, suggesting sex differences in terms of fitness and evolutionary function among these compounds. Pollen from male flowers is wind-dispersed for the fertilization of female cones, which then produce seeds. In most regions worldwide, male H. lupulus plants are physically removed from commercial hop growing areas to prevent pollination; pollinated seeds are undesirable for brewing beer because they possess smaller amounts of essential oils and resins, and seed fatty acids oxidation leads to off flavors in beer. However, male H. lupulus plants are essential for cultivating new varieties through hybridization. Hops have been used in brewing for centuries for their characteristic aroma and bitter taste. Phytochemical studies have revealed that hops contain several components such as amino acids, cellulose, essential oils, lipids, pectins, proteins, polyphenols, resins, and waxes. Dried hops contain 4−14% polyphenols, 15−30% resins, and 0.5−3% essential oils, amounting to over 1000 different components in the hop oil fraction.15,16 The content range of dried hop cone functional components is shown in Table 1. Among these components, α-
aroma hop
bittering hop
dual-purpose hop
constituent
amount (w/w %) 2−7 2−10 0.5−3.0 3−6 0.1 15
Ahtanum Amethyst Aramis Archer Barbe Rouge Crystal Delta East Kent Goldings Fuggles Fuggles Goldings Hersbrucker Apollo Boadicea Bravo Brewers Gold Bullion Bullion UK Chelan Galena Agnus Azacca Calypso Chinook Citra Columbus Dr Rudi Eagle EI Dorado Eureka Eureka! Galaxy Green Bullet Herkules Admiral
Table 1. Functional Components in Dried Hop Cones39 α-acids β-acids essential oils polyphenols amino acids protein
name
alpha acid (%)
couhmulone
USA Czech Republic France UK France USA USA UK
5−8 3.5−6
30−35 20−25
6−8 4−6 7−10 3−6 3−6 5−8
21−22 32−38 24−28 20−26 22−24 26−32
UK Belgium Belgium Germany USA UK USA France, Germany USA UK USA USA Czech Republic USA USA USA USA USA New Zealand Slovenia USA Slovenia USA Australia New Zealand Germany UK
4−7 4−7 4−8 2−4 15−19 6−9 14−18 5−9
29−30 29−30 20−35 17−25 24−28 21−27 29−34 40−48
8−11 8−11 12−15 10−14 12−14
35−40 35−40 33−35 36−40 29−38
14−16 11−14 11−15 11−14 14−20 11−14 12−17 13−17 11−17 17−20 13−15 10−13 16−20 14−16
16−18 40−42 29−35 22−24 28−32 36−39 20−23 28−33 21−25 28−30 32−35 41−43 32−38 37−45
country
sometimes not strictly divided by 5%. For example, Barbe Rouge, which is classified as aroma hops, contains 7−10% αacid.6 Aroma and bitterness flavors in beer are also influenced by dry-hopping techniques. Volatile oils are easily lost or altered during storage and boil out of the wort quickly during the late boil.21 Therefore, improvements to dry-hopping technology are important for preserving volatile oils. Dry-hopping originally consisted of adding hops plugs immediately prior to serving beer; modern techniques include adding hops plugs at the end of the boiling or cold stages, to the primary or secondary fermenter, or directly to the keg.22 Adding hops plugs to the secondary fermenter prevents the proliferation of bacteria on unsterilized hops due to low pH and alcohol levels; because this stage occurs after primary CO2 formation, this technique also prevents hops aromas from boiling off. This dry-hopping technique is increasingly prevalent in commercial breweries because it plays an important role in preserving volatile oil aromas, and increases α-acid and xanthohumol levels, which influence the biological activity of beer.20,23 For example, combining different varieties of hops and dry-hopping
acids, volatile oil, β-acids, metals, polyphenols, and single nucleotide polymorphism (SNP) markers can be used to classify hop varieties and geographical origins.17−19 According to their α-acid concentrations, hops can be divided into three categories: aroma, bitter, and dual-purpose hops (Table 2.). Aroma hops, generally used for conditioning, are rich in volatile oils associated with good aroma and flavor, but have a lower α-acid percentage (
