Scope Xanthohumol (XN) is a bioactive prenylflavonoid from hops. A single-dose pharmacokinetic (PK) study was conducted in men (n=24) and women (n=24) to determine dose-concentration relationships. Methods and results Subjects received a single oral dose of 20, 60, or 180 mg XN. Blood was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 h. Plasma levels of XN and its metabolites, isoxanthohumol (IX), 8-prenylnaringenin (8PN) and 6-prenylnaringenin (6PN) were measured by LC-MS/MS. Xanthohumol and IX conjugates were dominant circulating flavonoids among all subjects. Levels of 8PN and 6PN were undetectable in most subjects. The XN PK profile showed peak concentrations around 1h and between 4-5h after ingestion. The maximum XN concentrations (Cmax) were 45±7 μg/L, 67±11 μg/L, and 133±23 μg/L for the 20, 60, and180 mg dose, respectively. Using non-compartmental modeling, the area under the curves (AUC0→∞) for XN were 92±68 h×μg/L, 323±160 h×μg/L, and 863±388 h×μg/L for the 20, 60, and 180 mg dose, respectively. The mean half-life of XN was 20 h for the 60 and 18 h for the 180 mg dose. Conclusion Xanthohumol has a distinct biphasic absorption pattern with XN and IX conjugates being the major circulating metabolites.

Because of their weakly estrogenic properties, interest in nonylphenol polyethoxylates and their carboxylated metabolites is resurging. To assess their occurrence in surface waters impacted by municipal and industrial effluents, an analytical method was developed for the quantitative determination of nonylphenol polyethoxy carboxylate (NPEC) metabolites of nonylphenol polyethoxylate surfactants in paper mill effluents, municipal sewage treatment plant effluents, and river waters. Strong anion exchange solid phase extraction disks were used for NPEC isolation from aqueous samples, and NPEC elution from the disk is simultaneously combined with derivatization. Extracts were analyzed by gas chro matography and positive mode chemical ionization mass spectrometry. The detection limit of the method ranged from 0.2 μg/L for NP1EC to 2 μg/L for NP4EC. The total concentration of NPECs in a group of paper mill and municipal sewage effluents ranged from below detection to 1300 μg/L. The total concentration of NPECs in several river waters ranged from below detection to 13.8 μg/L.

Scope Xanthohumol (XN), a dietary flavonoid found in hops, may have health protective actions against cardiovascular disease and type 2 diabetes. Yet, there are limited data on the pharmacokinetics (PK) of XN. This study provides PK parameters for XN and its major metabolites in rats. Methods and results A pharmacokinetic study was conducted in male jugular vein-cannulated Sprague-Dawley rats. Rats (n=12/group) received an intravenous (IV) injection (1.86 mg/kg BW) or an oral gavage of a low (1.86 mg/kg BW), medium (5.64 mg/kg BW), or high (16.9 mg/kg BW) dose of XN. Plasma samples were analyzed for XN and its metabolites using LC-MS/MS. The maximum concentration (Cmax) and area under the curve (AUC0-96 h) of total XN (free and conjugated) were 2.9 ± 0.1 mg/L and 2.5 ± 0.3 h*mg/L in the IV group, 0.019 ± 0.002 mg/L and 0.84 ± 0.17 h*mg/L in the oral low group, 0.043 ± 0.002 mg/L and 1.03 ± 0.12 h*mg/L in the oral medium group, and 0.15 ± 0.01 mg/L and 2.49 ± 0.10 h*mg/L in the oral high group. Conclusion The bioavailability of XN is dose-dependent and approximately 0.33, 0.13 and 0.11 in rats, for the low, medium and high dose groups, respectively.

Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN. We compared their effects to those of XN by feeding C57BL/6J mice a high-fat diet (HFD) containing XN, DXN, or TXN for 13 weeks. DXN and TXN were present at higher concentrations than XN in plasma, liver and muscle. Mice administered XN, DXN or TXN showed improvements of impaired glucose tolerance compared to the controls. DXN and TXN treatment resulted in a decrease of HOMA-IR and plasma leptin. C2C12 embryonic muscle cells treated with DXN or TXN exhibited higher rates of uncoupled mitochondrial respiration compared to XN and the control. Finally, XN, DXN, or TXN treatment ameliorated HFD-induced deficits in spatial learning and memory. Taken together, DXN and TXN could ameliorate the neurocognitive-metabolic impairments associated with HFD-induced obesity without risk of liver injury and adverse estrogenic effects.

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