Method Development and Validation for Ultra-High-Pressure LC/MS/MS Determination of Hop Prenylflavonoids in Human Serum

Yuan, Yue; Qiu, Xi; Nikolić, Dejan; Dahl, Jeffrey H.; Breemen, Richard B. van

doi:10.5740/jaoacint.11-542

Cited by 16 publications

(14 citation statements)

References 18 publications

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“…) that can cyclize to form the flavonoid IX in the intestine or in the presence of gastric acid in the stomach , conversion probably occurred to a major extent in the gastrointestinal system during absorption. It should be noted that conversion of XN to IX in serum during storage and preparation prior to analysis has been investigated and determined to be insignificant .…”

Section: Resultsmentioning

confidence: 99%

“…XN, IX, 8‐PN, and 6‐PN were measured in human serum using a validated ultrahigh‐pressure LC‐MS/MS (UHPLC‐MS/MS) method that was reported previously . Urine samples were measured using a variation of this method with the following changes.…”

Section: Methodsmentioning

confidence: 99%

“…Each residue was reconstituted in 100 μL of 70% aqueous methanol. The concentrations of XN, IX, 8‐PN, and 6‐PN in the urine extracts were then measured using UHPLC/MS‐MS as on a Shimadzu LCMS‐8030 triple quadrupole mass spectrometer equipped with a Nexera UHPLC system and a Shim‐pack XR‐ODS III (2.0 × 50 mm, 1.6 μm) C 18 column as described for serum analysis .…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops

Breemen

Yuan

Banuvar

et al. 2014

Molecular Nutrition Food Res

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151

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SCOPE Women seeking alternatives to hormone replacement therapy for menopausal symptoms often try botanical dietary supplements containing extracts of hops (Humulus lupulus L.). Hops contain 8-prenylnaringenin (8-PN), a potent phytoestrogen, the related flavanones 6-prenylnaringenin (6-PN) and isoxanthohumol (IX), and the prenylated chalcone xanthohumol (XN). METHODS AND RESULTS After chemically and biologically standardizing an extract of spent hops to these marker compounds, an escalating dose study was carried out in menopausal women to evaluate safety and pharmacokinetics. 8-PN, 6-PN, IX, and XN, sex hormones, and prothrombin time (PT/INR) were determined in blood samples and/or 24-h urine samples. There was no effect on sex hormones or blood clotting. The maximum serum concentrations of the prenylated phenols were dose-dependent and were reached from 2 to 7 h, indicating slow absorption. The marker compounds formed glucuronides that were found in serum and urine. Secondary peaks at 5 h in the serum concentration-time curves indicated enterohepatic recirculation. The serum concentration-time curves indicated demethylation of IX to form 8-PN and cyclization of XN to IX. Slow absorption and enterohepatic recirculation contributed to half-lives exceeding 20 h. CONCLUSION This human study indicated long half-lives of the estrogenic and proestrogenic prenylated phenols in hops but no acute toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops

Breemen

Yuan

Banuvar

et al. 2014

Molecular Nutrition Food Res

Self Cite

151

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“…Quantitative analyses of marker compounds in serum were carried out as reported previously (van Breemen et al, 2014; Yuan et al, 2012). Briefly, 0.2 ml of serum was diluted with 0.2 ml of 0.1 M sodium acetate buffer pH 5.0 containing 8-isopentyl naringenin as internal standard and then incubated with 500 units of β-glucuronidase for 3 h at 37 °C to release free aglycones from glucuronic acid conjugates.…”

Section: Methodsmentioning

confidence: 99%

A standardized Humulus lupulus (L.) ethanol extract partially prevents ovariectomy-induced bone loss in the rat without induction of adverse effects in the uterus

et al. 2017

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Background Hops (Humulus lupulus (L.)) dietary supplements are of interest as herbal remedies to alleviate menopausal symptoms, such as hot flushes, depression and anxiety. So far, the evidence regarding estrogenic and related properties of hops preparations has been considered insufficient for a market authorization for menopausal indications. Purpose The study aims to investigate a chemically standardized hops extract regarding its safety in the uterus, as wells as its efficacy to prevent bone loss in the ovariectomized rat model. Study Design/Methods Female Wistar rats were ovariectomized and divided into a control group receiving phytoestrogen-free diet, a group treated with E2benzoate (0.93 mg/kg body weight/d) and a group treated with the standardized hops extract (60 mg/kg body weight/d) for 8 weeks. Micro-computed tomography of the tibiae and vertebrae, as wells as histological changes in the uterus and tibia were analyzed. Results Neither uterotrophic nor proliferative effects were observed in the endometrium in response to the oral 8-week administration of the hops extract. However, site-dependent skeletal effects were observed. The hops extract significantly decreased the number of osteoclasts in the tibial metaphysis and prevented reduction of the trabecular thickness that resulted from estradiol depletion. In contrast, the hops extract did not prevent the ovariectomy-induced micro-architectural changes in the lumbar vertebra. Certain parameters (e.g. thickness and number of trabeculae) were even found to be below the values determined in the ovariectomized control group. Conclusion Taken together, the results provide evidence for the safety of the standardized hops extract and point to a weak bone type-specific, protective effect on bone loss following estradiol depletion.

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“…Quantitative analyses of marker compounds in serum were carried out as reported previously [28,29]. Briefly, 0.2 mL of serum was diluted with 0.2 mL of 0.1 M sodium acetate buffer pH 5.0 containing 8-isopentyl naringenin as internal standard and then incubated with 500 units of β-glucuronidase for 3 h at 37 °C to release free aglycones from glucuronic acid conjugates.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of estrogenic potency of a standardized hops extract on mammary gland biology and on MNU-induced mammary tumor growth in rats

Keiler

Macejova

Dietz

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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Supplements with estrogenic activities are intensively investigated as potential alternatives for the treatment of menopausal symptoms. These investigations include studies on their safety regarding potential breast cancer risks. Therefore, the aim of this study was to assess whether or not a standardized hops (Humulus lupulus) extract, containing 0.42% of the estrogenic flavanone, 8-prenylnaringenin, would stimulate growth of methyl-nitrosourea (MNU) induced mammary cancer in ovariectomized (OVX) Sprague-Dawley (SD) rats or would impact on the proliferative activity within the normal mammary gland of Wistar rats. To induce tumorigenesis SD-rats received an intraperitoneal injection of 50 mg/kg body weight of MNU on postnatal days PND 50 and 52. 28 days later animals were OVX or were SHAM operated (positive control) and randomly allocated and maintained for 140 days on either a phytoestrogen-free placebo diet (SHAM and negative control) or on the hops fortified diet. For the investigations in the normal mammary gland young adult Wistar rats were bilaterally OVX and randomly allocated to a control group fed to a phytoestrogen-free diet, or to a diet supplemented either with E2-benzoate or the hops extract. As a major result, the tumor incidence was 15% (3 tumors totally) in OVX controls, whereas it was 85% (39 tumors totally) in SHAM operated positive controls. No tumors were detectable in the hops group. In addition, no estrogenic activity of the hops extract was detectable in uterus and liver of these animals. In investigations on the normal mammary gland, no impact of hops extract on the expression of estrogen dependent proliferation markers or of progesterone receptor became apparent. In conclusion, the lack of growth stimulation of MNU-induced breast cancer in OVX SD-rats and the lack of stimulation proliferative events in the normal mammary gland of OVX Wistar rats by standardized hops extracts provides an important piece of evidence regarding the safety of these extracts in the management of menopausal symptoms.

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Method Development and Validation for Ultra-High-Pressure LC/MS/MS Determination of Hop Prenylflavonoids in Human Serum

Cited by 16 publications

References 18 publications

Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops

Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops

A standardized Humulus lupulus (L.) ethanol extract partially prevents ovariectomy-induced bone loss in the rat without induction of adverse effects in the uterus

Evaluation of estrogenic potency of a standardized hops extract on mammary gland biology and on MNU-induced mammary tumor growth in rats

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