The Multiple Biological Targets of Hops and Bioactive Compounds

Abstract

Botanical dietary supplements for women's health are increasingly popular. Older women tend to take botanical supplements such as hops as natural alternatives to traditional hormone therapy to relieve menopausal symptoms. Especially extracts from spent hops, the plant material remaining after beer brewing, are enriched in bioactive prenylated flavonoids that correlate with the health benefits of the plant. The chalcone xanthohumol (XH) is the major prenylated flavonoid in spent hops. Other less abundant but important bioactive prenylated flavonoids are isoxanthohumol (IX), 8-prenylnaringenin (8-PN), and 6-prenylnaringenin (6-PN). Pharmacokinetic studies revealed that these flavonoids are conjugated rapidly with glucuronic acid. XH also undergoes phase I metabolism in vivo to form IX, 8-PN, and 6-PN. Several hop constituents are responsible for distinct effects linked to multiple biological targets, including hormonal, metabolic, inflammatory, and epigenetic pathways. 8-PN is one of the most potent phytoestrogens and is responsible for hops' estrogenic activities. Hops also inhibit aromatase activity, which is linked to 8-PN. The weak electrophile, XH, can activate the Keap1-Nrf2 pathway and turn on the synthesis of detoxification enzymes such as NAD(P)H-quinone oxidoreductase 1 and glutathione S-transferase. XH also alkylates IKK and NF-κB, resulting in anti-inflammatory activity. Antiobesity activities have been described for XH and XH-rich hop extracts likely through activation of AMP-activated protein kinase signaling pathways. Hop extracts modulate the estrogen chemical carcinogenesis pathway by enhancing P450 1A1 detoxification. The mechanism appears to involve activation of the aryl hydrocarbon receptor (AhR) by the AhR agonist, 6-PN, leading to degradation of the estrogen receptor. Finally, prenylated phenols from hops are known inhibitors of P450 1A1/2; P450 1B1; and P450 2C8, 2C9, and 2C19. Understanding the biological targets of hop dietary supplements and their phytoconstituents will ultimately lead to standardized botanical products with higher efficacy, safety, and chemopreventive properties.

A Review of the Potential Health Benefits of Low Alcohol and Alcohol-Free Beer: Effects of Ingredients and Craft Brewing Processes on Potentially Bioactive Metabolites

“…The potential for hops as a source of bioactives, including polyphenols, is considerable [14], leading to a number of potential targets that may be affected via hormonal mechanisms, as some of the bioactives can mimic estrogen, whilst others may function via antioxidant mechanisms or through altering metabolism to enhance the metabolism of xenobiotics and even regulate lipid metabolism.…”

“…This has led to considerable interest in the hop, not only for its flavor and aromatic properties in beer, but as a potential nutritional supplement. This is because hops, which generally refers to the female flower cones of the plant, have been found to be a rich source of prenylated phenols, including chalcones and flavonoids (some of which are classed phytoestrogens) [14]. It has been proposed that the estrogen-modulating effects of hops and their extracts are due to the effects of them being antagonists and binding to the estrogen receptor, preventing the action of estrogen, as well as the potential to inhibit aromatase, which is the rate limiting step in the synthesis of estrone and estradiol (E 2 ).…”

“…It has been proposed that the estrogen-modulating effects of hops and their extracts are due to the effects of them being antagonists and binding to the estrogen receptor, preventing the action of estrogen, as well as the potential to inhibit aromatase, which is the rate limiting step in the synthesis of estrone and estradiol (E 2 ). This has led to the emergence of hop-based products as potential supplements to support women going through the menopause [14].…”

Dietary natural flavonoids treating cancer by targeting aryl hydrocarbon receptor

“…In addition, Choi et al claimed that b-naphthoflavone, as a nontoxic flavonoid, can induce the detoxification potential of the representative detoxification enzyme cytochrome P4501A1 (Chuang et al 2012). Subsequently, Bolton et al reported that a potent AhR agonist 6-Prenylnarigenin in hops, resulting in a selective up-regulation of the P450 1A1-mediated estrogen detoxification pathway (Bolton et al 2019). Of note, some flavonoids that bind to AhR elicit antagonism rather than increase CYP1 activity.…”

New Tools for Hop Cytogenomics: Identification of Tandem Repeat Families from Long-Read Sequences ofHumulus lupulus

“…Humulus lupulus (hop) is a dioecious twining bine in the Cannabaceae family of flowering plants with a long history of cultivation (Neve, 1991;Moir, 2000) for various uses including medicine (as reviewed by Ososki and Kennelly, 2003;Bolton et al, 2019) and animal fodder (Siragusa et al, 2008), but is most commonly known as a flavoring agent in the brewing industry. The quest for complex taste and aromas in the rapidly expanding craft brewing industry has placed increasing demands on breeders to produce new varieties of plants with specific desirable traits as well as disease resistance (Kavalier et al, 2011;Easterling et al, 2018;Yan et al, 2019).…”