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Planta Med 2015; 81(12/13): 1182-1189
DOI: 10.1055/s-0035-1545980
Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Structure-Dependent Deconjugation of Flavonoid Glucuronides by Human β-Glucuronidase – In Vitro and In Silico Analyses[*]

Monika Untergehrer
1   Department of Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany
,
Daniel Bücherl
1   Department of Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany
,
Hans-Joachim Wittmann
2   Department of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany
,
Andrea Strasser
2   Department of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany
,
Jörg Heilmann
1   Department of Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany
,
Guido Jürgenliemk
1   Department of Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany
› Author Affiliations
Further Information

Publication History

received 13 January 2015
revised 04 March 2015

accepted 28 March 2015

Publication Date:
27 May 2015 (online)

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Abstract

Flavonoid glycosides are extensively metabolized to glucuronidated compounds after oral intake. Recently, a cleavage of quercetin glucuronides by β-glucuronidase has been found. To characterize the deglucuronidation reaction and its structural prerequisites among the flavonoid subtypes more precisely, four flavonol glucuronides with varying glucuronidation positions, five flavone 7-O-glucuronides with varying A- and B-ring substitution as well as one flavanone- and one isoflavone-7-O-glucuronide were analyzed in a human monocytic cell line. Investigation of the deglucuronidation rates by HPLC revealed a significant influence of the glucuronidation position on enzyme activity for flavonols. Across the flavonoid subtypes, the C-ring saturation also showed a significant influence on deglucuronidation, whereas A- and B-ring variations within the flavone-7-O-glucuronides did not affect the enzymesʼ activity. Results were compared to computational binding studies on human β-glucuronidase. Additionally, molecular modeling and dynamic studies were performed to obtain detailed insight into the binding and cleavage mode of the substrate at the active site of the human β-glucuronidase.

Key words

deglucuronidation - flavonoid glucuronides - inflammation - monocytes - molecular dynamics

* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.


Supporting Information

 

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