Comparison of the in Vitro Estrogenic Activities of Compounds from Hops (<i>Humulus lupulus</i>) and Red Clover (<i>Trifolium pratense</i>)

Overk, Cassia R.; Yao, Ping; Chadwick, Lucas R.; Nikolić, Dejan; Sun, Yongkai; Cuendet, Muriel; Deng, Yunfan; Hedayat, A.; Pauli, Guido F.; Farnsworth, Norman R.; Breemen, Richard B. van; Bolton, Judy L.

doi:10.1021/jf050448p

Cited by 108 publications

(125 citation statements)

References 54 publications

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“…(5). These results are consistent with previously reported screening studies of hop extracts [18], which found that 8-prenylnaringenin was the most potent estrogen in hop extracts.…”

Section: Screening Of Botanical Extractssupporting

confidence: 93%

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Development of a Screening Assay for Ligands to the Estrogen Receptor Based on Magnetic Microparticles and LC-MS

Choi¹,

Breemen²

2008

CCHTS

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A high throughput screening assay for the identification of ligands to pharmacologically significant receptors was developed based on magnetic particles containing immobilized receptors followed by liquid chromatography-mass spectrometry (LC-MS). This assay is suitable for the screening of complex mixtures such as botanical extracts. For proof-of-principle, estrogen receptor-α (ER-α) and ER-β were immobilized on magnetic particles functionalized with aldehyde or carboxylic acid groups. Alternatively, biotinylated ER was immobilized onto streptavidin-derivatized magnetic particles. The ER that was immobilized using the streptavidin-biotin chemistry showed higher activity than that immobilized on aldehyde or carboxylic acid functionalized magnetic particles. Immobilized ER was incubated with extracts of Trifolium pratense L. (red clover) or Humulus lupulus L. (hops).As a control for non-specific binding, each botanical extract was incubated with magnetic particles containing no ER. After magnetic separation of the particles containing bound ligands from the unbound components in the extract, the particles were washed, ligands were released using methanol, and then the ligands were identified using LC-MS. The estrogens genistein and daidzein were identified in the red clover extract, and the estrogen 8-prenylnaringenin was identified in the hop extract. These screening results are consistent with those obtained using previous screening approaches.

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“…(5). These results are consistent with previously reported screening studies of hop extracts [18], which found that 8-prenylnaringenin was the most potent estrogen in hop extracts.…”

Section: Screening Of Botanical Extractssupporting

confidence: 93%

“…Centrifugal ultrafiltration filters (Microcon YM-30) were purchased from Millipore (Bedford, MA). Ethanolic extracts of the aerial parts of red clover, Trifolium pratense L., and hop cones, from Humulus lupulus L., were prepared as described previously [18].…”

Section: Methodsmentioning

confidence: 99%

Development of a Screening Assay for Ligands to the Estrogen Receptor Based on Magnetic Microparticles and LC-MS

Choi¹,

Breemen²

2008

CCHTS

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“…Furthermore, 8-PN and IX were also evaluated since 8-PN is the major active phytoestrogen in H. lupulus [16,17,20,21], and IX can be metabolized to 8-PN [22]. The major phytoestrogens in T. pratense, daidzein and genistein, and their metabolic precursors, formononetin and biochanin A, were not evaluated since there is already a large body of data on these compounds [36,37], and the primary focus was on H. lupulus.…”

Section: Discussionmentioning

confidence: 99%

“…The most potent estrogen in H. lupulus is 8-PN, which is in actuality an artifact formed through isomerization of the precursor chalcone, desmethylxanthohumol [18,19]. 8-Prenylnaringenin has been shown in a variety of in vitro assays to be estrogenic in the nanomolar range [16,17,20,21]. It can also be formed from precursors such as IX, and xanthohumol (XH), through metabolism [22].…”

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confidence: 99%

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

Overk

Guo

Chadwick

et al. 2008

Chemico-Biological Interactions

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The lack of a safe and reliable alternative to hormone therapy (HT) for treating menopausal symptoms underscores the need for alternative therapies. OBJECTIVE: The purpose of this study was to assess the in vivo estrogenic effects of the botanical dietary supplements Trifolium pratense (red clover) and Humulus lupulus (hops), and two compounds obtained from H. lupulus, isoxanthohumol and 8-prenylnaringenin (8-PN) using the ovariectomized uterotrophic adult rat model. A H. lupulus extract and a 30% isoflavone extract of T. pratense were tested at three escalating doses as was one dose of isoxanthohumol for 21 days. 8-Prenylnaringenin, the major estrogen in H. lupulus, was also tested at three relevant escalating doses. In order to determine the in vivo metabolism of 8-PN, the major Phase I and Phase II metabolites were also identified. The primary outcome measure, uterus weight gain, indicated that H. lupulus and T. pratense did not have an estrogenic effect on the uterus, and none of the secondary outcome measures were positive. In contrast, there was a clear dose response when 8-PN was evaluated where the middle and high doses of 8-PN were active. 8-Prenylnaringenin in rat plasma, liver, and mammary gland was measured and the major Phase I and Phase II 8-PN metabolites were detected. Our findings suggest that while both the H. lupulus and T. pratense extracts do not have an effect on the rat uterus, 8-PN at equivalent doses to those previously used in humans did have an effect, and may therefore have a deleterious effect in women. IntroductionSymptoms associated with menopause such as insomnia, loss of libido, vaginal atrophy, depression, and hot flashes can greatly affect the quality of life for women. Many women have used hormone therapy (HT) to alleviate menopausal symptoms; however, with the publication The strobiles of Humulus lupulus L. (Cannabaceae) (hops) are primarily used to flavor beer, and have been studied since 1953 for a potential estrogenic mechanism of action [13][14][15]. In the past, the flavonoids 8-PN and 6-PN, and the chalcone, isoxanthohumol (IX), have been isolated and reported to be estrogenic in vitro and/or in vivo [16,17]. The most potent estrogen in H. lupulus is 8-PN, which is in actuality an artifact formed through isomerization of the precursor chalcone, desmethylxanthohumol [18,19]. 8-Prenylnaringenin has been shown in a variety of in vitro assays to be estrogenic in the nanomolar range [16,17,20,21]. It can also be formed from precursors such as IX, and xanthohumol (XH), through metabolism [22].In previous metabolic studies, it has been shown that human liver microsomes convert 8-PN to 12 metabolites [22]. Among them, are the most abundant monooxygenated metabolites (Figure 1). The estrogenicities of the 8-PN alcohols have been previously determined [23] and were found to be ∼10 fold less estrogenic than 8-PN. Phase II metabolites of 8-PN, including glucuronides and sulfate conjugates, have been identified in incubations with human Caco-2 cells and human hepatocytes [2...

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“…Secondary metabolites are known for their strong biological activity, including improvement of quality of both human and animal diet. It is known that red clover isoflavones are used in HRT, for the prevention of diseases that occur in menopause in women (Overk et al, 2005). In the study by Oleszek et al (2007) it was discovered that the species T. heldreichianum, T. scabrum and T. subterraneum have extremely high content of isoflavones (more than red clover), which indicates the necessity of studying the representatives of this genus in wild flora.…”

Section: Introductionmentioning

confidence: 99%

Quality Parameters and Antioxidant Activity of Three Clover Species in Relation to the Livestock Diet

Petrović

Stanković

Anđelković

et al. 2016

Not Bot Horti Agrobo

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Products of metabolism that are directly involved in growth, development and reproduction and also secondary products of metabolism were studied in 16 natural populations of three species of the genus Trifolium (T. repens -four populations, T. alpestre -three populations, T. pannonicum -nine populations), collected from the central Balkans region, i.e. territory of Serbia. Statistical analysis showed the presence of variability in all species of the test material. The best quality of dry matter, estimated by the ratio of crude protein and crude fiber, was achieved in the populations of white clover. In this species, average protein content was 216.4 g kg . It can be concluded that the selection of these populations may lead to creation of different varieties of fodder crops that could give safe animal feed and would be suitable for growing under adverse conditions of mountainous climate.

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Comparison of the in Vitro Estrogenic Activities of Compounds from Hops (Humulus lupulus) and Red Clover (Trifolium pratense)

Cited by 108 publications

References 54 publications

Development of a Screening Assay for Ligands to the Estrogen Receptor Based on Magnetic Microparticles and LC-MS

Development of a Screening Assay for Ligands to the Estrogen Receptor Based on Magnetic Microparticles and LC-MS

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

Quality Parameters and Antioxidant Activity of Three Clover Species in Relation to the Livestock Diet

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