Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC‐MS/MS

Abstract

Xanthohumol, a natural isoflavone from Humulus lupulus L., possesses biological activities. However, the biological fate of xanthohumol in vivo remains unclear. The aim of this study was to investigate the absorption and metabolism of xanthohumol in rats through UPLC-MS/MS. The plasma, urine and fecal samples were collected after oral administration of xanthohumol (25, 50, 100 mg/kg) in SD rats. The contents of xanthohumol and its metabolites were determined by UPLC-MS/MS. A total of 6 metabolites of xanthohumol were identified in rats, including methylated, glucuronidated, acid-catalyzed cyclization and oxidation, indicating xanthohumol underwent phase I and II metabolism. Besides, isoxanthohumol was the major metabolites of xanthohumol. Xanthohumol was rapidly absorbed, metabolized, and eliminated in rats. The pharmacokinetics results showed the T max of xanthohumol and isoxanthohumol were 3 and 2.33 h, respectively. The AUC 0−t of xanthohumol and isoxanthohumol were 138.83 � 6.03 and 38.77 � 4.46 ng/ml•h, respectively. Furthermore, xanthohumol was mainly excreted in the form of prototype through feces and a small amount of xanthohumol was excreted through urine. These results illustrated the absorption, metabolism, and pharmacokinetics process of xanthohumol in rats, and provided a reference for the further rational applications.

Tissue distribution and pharmacokinetics of isoxanthohumol from hops in rodents

“…We also tried to confirm the presence of 6‐PN in the samples analyzed in this study by using a reference standard, but it was not detected (data not shown). Other studies revealed that 6‐PN was not detected in the plasma of rats (Legette et al., 2012 ) or human subjects (Legette et al., 2014 ) who ingested xanthohumol, but was confirmed in feces (Bai et al., 2022 ). Although we did not analyze the feces, our data inferred that there was minimal to no 6‐PN circulation in the body after IXA ingestion.…”

“…After oral ingestion, xanthohumol was found in epithelial cells in the gastrointestinal tract (Wolff et al., 2011 ) and in breast tissues (Karabin et al., 2015 ). Because the metabolites of xanthohumol are mainly excreted into the feces (Bai et al., 2022 ), future studies should detect IXA in the digestive tract and feces for comparison purposes. Further study will be needed to clarify these issues and improve our knowledge of IXA tissue distribution so it can be used as a nutraceutical.…”

Stepwise Targeted Matching Strategy for Comprehensive Profiling of Xanthohumol Metabolites In Vivo and In Vitro Using UHPLC-Q-Exactive Orbitrap Mass Spectrometer

“…Few studies reported metabolites in both phases I and Ⅱ comprehensively at the same time. Only six metabolites of XN were identified in the plasma, urine, and feces samples of rats by Bai et al [ 36 ], including methylated, glucuronidated, acid-catalyzed cyclization, and oxidation. However, in our study, we identified 53 XN metabolites, of which some simultaneously possess two glucuronides-bounding or glucuronides and sulfating-bounding, which indicated our method was superior to the method that has been reported.…”