Synthesis of Human Phase I and Phase II Metabolites of Hop (Humulus lupulus) Prenylated Flavonoids

Metabolites

卷:12

Michael Rychlik¹  Lance Buckett¹  Veronika Spindler¹  Sabrina Schönberger¹  Christian Schoergenhofer²  Nadine Sus³  Jan Frank³  Oliver Frank⁴ 

[1] Analytical Food Chemistry, Technical University of Munich, Maximus-von-Imhof Forum 2, 85354 Freising, Germany;

[2] Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria;

[3] Department of Food Biofunctionality (140b), Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 28, 70599 Stuttgart, Germany;

[4] Food Chemistry and Molecular Sensory Science, Technical University of Munich, Lise-Meitner-Str. 34, 85354 Freising, Germany;

关键词: metabolites;    synthesis;    prenylated flavonoids;    hops;    beer;    xanthohumol;   

DOI  :  10.3390/metabo12040345

来源: DOAJ

【 摘 要 】

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood.

【 授权许可】

Unknown