Abstract
Quercetin-3-glucuronide (Q3GA), the main phase II metabolite of quercetin (Q) in human plasma, is considered to be a more stable form of Q for transport with the bloodstream to tissues, where it can be potentially deconjugated by β-glucuronidase (β-Gluc) to Q aglycone, which easily enters the brain. This study evaluates the effect of lipopolysaccharide (LPS)-induced acute inflammation on β-Gluc gene expression in the choroid plexus (ChP) and its activity in blood plasma, ChP and cerebrospinal fluid (CSF), and the concentration of Q and its phase II metabolites in blood plasma and CSF. Studies were performed on saline- and LPS-treated adult ewes (n = 40) receiving Q3GA intravenously (n = 16) and on primary rat ChP epithelial cells and human ChP epithelial papilloma cells. We observed that acute inflammation stimulated β-Gluc activity in the ChP and blood plasma, but not in ChP epithelial cells and CSF, and did not affect Q and its phase II metabolite concentrations in plasma and CSF, except Q3GA, for which the plasma concentration was higher 30 min after administration (p < 0.05) in LPS- compared to saline-treated ewes. The lack of Q3GA deconjugation in the ChP observed under physiological and acute inflammatory conditions, however, does not exclude its possible role in the course of neurodegenerative diseases.
Highlights
We demonstrated in an ovine model that the main metabolites of dietary Q in cerebrospinal fluid (CSF) are
In the present study, we aimed to evaluate the effect of LPS-induced acute inflammation on: (1) β-Gluc gene expression in the choroid plexus (ChP) and its activity in blood plasma, the ChP and CSF; and (2) concentration of Q and its phase II
We examined β-Gluc expression and activity, as well as Q3GA accumulation separately in the epithelial cells of the ChP under basal and LPS-challenged conditions
Summary
Quercetin (Q) is the most abundant dietary flavonoid, and its anti-oxidative and antiinflammatory actions have been demonstrated in both in in vitro and in vivo conditions [1,2,3]. Via the epithelium of the choroid plexus (ChP) [5]. It was previously found in in vitro studies using BBB models that Q enters the brain [6,7]. The dietary Q occurs mainly as glycosides and, after hydrolysis to free Q aglycone in the gastro-intestinal tract, is rapidly metabolized via the phase II detoxification pathway (glucuronidation, methylation and sulphation), before reaching the target tissue, to less active or inactive metabolites, and in this form is rapidly excreted via urine and bile [8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
