Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats
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Authors
Zabela, Volha
Sampath, Chethan
Oufir, Mouhssin
Moradi-Afrapoli, Fahimeh
Butterweck, Veronika
Hamburger, Matthias
Author (Corporation)
Publication date
12.2016
Typ of student thesis
Course of study
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Fitoterapia
Special issue
DOI of the original publication
Link
Series
Series number
Volume
115
Issue / Number
Pages / Duration
189-197
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
SCOPE:
Kaempferol is a major flavonoid in the human diet and in medicinal plants. The compound exerts anxiolytic activity when administered orally in mice, while no behavioural changes were observed upon intraperitoneal administration, or upon oral administration in gut sterilized animals. 4-Hydroxyphenylacetic acid (4-HPAA), which possesses anxiolytic effects when administered intraperitoneally, is a major intestinal metabolite of kaempferol. Pharmacokinetic properties of the compounds are currently not clear.
METHODS AND RESULTS:
UHPLC-MS/MS methods were validated to support pharmacokinetic studies of kaempferol and 4-HPAA in rats. Non-compartmental and compartmental analyses were performed. After intravenous administration, kaempferol followed a one-compartment model, with a rapid clearance (4.40-6.44l/h/kg) and an extremely short half-life of 2.93-3.79min. After oral gavage it was not possible to obtain full plasma concentration-time profiles of kaempferol. Pharmacokinetics of 4-HPAA was characterized by a two-compartment model, consisting of a quick distribution phase (half-life 3.04-6.20min) followed by a fast elimination phase (half-life 19.3-21.1min).
CONCLUSION:
Plasma exposure of kaempferol is limited by poor oral bioavailability and extensive metabolism. Both compounds are rapidly eliminated, so that effective concentrations at the site of action do not appear to be reached. At present, it is not clear how the anxiolytic-like effects reported for the compounds can be explained.
Keywords
4-HPAA, Kaempferol, Pharmacokinetics, UHPLC-MS/MS
Subject (DDC)
Event
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ISBN
ISSN
1873-6971
0367-326X
0367-326X
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Zabela, V., Sampath, C., Oufir, M., Moradi-Afrapoli, F., Butterweck, V., & Hamburger, M. (2016). Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats. Fitoterapia, 115, 189–197. https://doi.org/10.1016/j.fitote.2016.10.008