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European Journal of Nutrition
Published in: European Journal of Nutrition 8/2008

01-12-2008 | ORIGINAL CONTRIBUTION

Dietary polyphenols identified as intracellular protein kinase A inhibitors

Authors: Jan Øivind Moskaug, Grethe I. Borge, Anne M. Fagervoll, Ingvild Paur, Harald Carlsen, Rune Blomhoff

Published in: European Journal of Nutrition | Issue 8/2008

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Abstract

Background

Dietary plants contain several thousands different polyphenols that can potentially influence normal and pathological cellular processes through modulation of intracellular signaling pathways. A few polyphenols have been shown to be potent inhibitors of protein kinases.

Aims of study

To identify possible dietary protein kinase A (PKA) inhibitors we designed a method for screening of substances in crude mixtures of food items for modulation of intracellular PKA activity that enables high-throughput testing of a large number of compounds and extracts.

Methods

Luciferase was mutated to render it sensitive to phosphorylation by PKA (luciferasePKA) and transfected into a human hepatoma cell line (HepG2). Cells were then treated with extracts from dietary plants, including berries, fruits and spices, and intracellular PKA-activity was assessed by change in bioluminescence in live cells by imaging.

Results

Several extracts were found to inhibit PKA activity in a 96-well platform high-throughput screen. Green tea, crowberry, clove and cinnamon extracts were found to reduce intracellular cAMP levels consistent with their ability to increase luminescence from luciferasePKA. Also pomegranate extract inhibited intracellular PKA and was used to estimate cellular association of polyphenols by HPLC and LC–MS. Pomegranate extract contains several anthocyanins, including delphinidin-3 glucoside. Delphinidin aglycone was found to inhibit cellular PKA activity in a concentration dependent manner. The inhibitory activity was found to be structure specific as a closely related compound to delphinidin had no activity.

Conclusion

The current work identify phytochemicals in crude extracts which modulate cell signaling through PKA in a way that facilitate high through-put screening to help elucidate how plant based diet reduce risks of chronic diseases.
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Metadata
Title
Dietary polyphenols identified as intracellular protein kinase A inhibitors
Authors
Jan Øivind Moskaug
Grethe I. Borge
Anne M. Fagervoll
Ingvild Paur
Harald Carlsen
Rune Blomhoff
Publication date
01-12-2008
Publisher
D. Steinkopff-Verlag
Published in
European Journal of Nutrition / Issue 8/2008
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-008-0749-0

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