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Xanthohumol (XN), a natural prenylated flavonoid extracted and isolated from the hop plant (Humulus lupulus), possesses diverse pharmacological activities. Although the metabolites of XN have been investigated in the previous study, a comprehensive metabolic profile has been insufficient in vivo or in vitro until now. The current study was aimed at systematically elucidating the metabolic pathways of XN after oral administration to rats. Herein, a UHPLC-Q-Exactive Orbitrap MS was adopted for the potential metabolites detection. A stepwise targeted matching strategy for the overall identification of XN metabolites was proposed. A metabolic net (53 metabolites included) on XN in vivo and in vitro, as well as the metabolic profile investigation, were designed, preferably characterizing XN metabolites in rat plasma, urine, liver, liver microsomes, and feces. On the basis of a stepwise targeted matching strategy, the net showed that major in vivo metabolic pathways of XN in rats include glucuronidation, sulfation, methylation, demethylation, hydrogenation, dehydrogenation, hydroxylation, and so on. The proposed metabolic pathways in this research will provide essential data for further pharmaceutical studies of prenylated flavonoids and lay the foundation for further toxicity and safety studies. [ABSTRACT FROM AUTHOR]

Liquiritin (LQ), a main component of liquorice, exerts various biological activities. However, insufficient attentions have been paid to the metabolism study on this natural compound until now. Our present study was conducted to investigate the LQ metabolites in rats urine, faeces and plasma using UHPLC-LTQ-Orbitrap mass spectrometer in both positive and negative ion modes. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC), multiple mass defect filters (MMDFs), neutral loss fragments (NLFs) and diagnostic product ions (DPIs) were utilised to screen and identify LQ metabolites from HR-ESI-MS to ESI-MSn stage. As a result, a total of 49 metabolites were detected and characterised unambiguously or tentatively. These metabolites were presumed to generate through glucuronidation, sulfation, deglucosylation, dehydrogenation, methylation, hydrogenation, hydroxylation, ring cleavage and their composite reactions. Our results not only provided novel and useful data to better understand the biological activities of LQ, but also indicated that the proposed strategy was reliable for a rapid discovery and identification drug-related constituents in vivo. [ABSTRACT FROM AUTHOR]

Both phloretin and phlorizin (phloretin 2′-O-glucoside) extracted from the peel of apples are attributed to particular flavonoid dihydrochalcones with multiple pharmacological activities. However, metabolite structural characterization of these two components, which may accumulate to exert their pharmacological effects, remains insufficient. The present study aimed to comparatively clarify the metabolic pathways of phloretin and phlorizin after oral administration individually to Sprague-Dawley (SD) rats. Therefore, a rapid, integrate and systematic analytical strategy based on characteristic fragment ion fishing was proposed for the screening and identification of metabolites coming from phloretin and phlorizin using UHPLC-Q-Exactive Orbitrap mass spectrometry in parallel reaction monitoring mode. As a result, a total of 50 phloretin metabolites and 52 phlorizin metabolites were individually identified from different biological samples including rat plasma, urine, and faeces. Moreover, glucuronidation, sulfation, carbonylation and hydrolyzation were revealed to be the main metabolic pathways of phlorizin, while decarbonylation, glucuronidation and sulfation were regarded as the predominant biotransformation pathways as for phloretin. This is the first systematic study on comparison of metabolic profiles of phlorizin and phloretin in disease states, which was helpful to declare the complicated structure activity relationships between phlorizin and phloretin and shed light to their action mechanism. [ABSTRACT FROM AUTHOR]