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European Journal of Nutrition

Erschienen in:

01.12.2008 | ORIGINAL CONTRIBUTION

Dietary polyphenols identified as intracellular protein kinase A inhibitors

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

Erschienen in: European Journal of Nutrition | Ausgabe 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 (luciferase^PKA) 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 luciferase^PKA. 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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Titel: Dietary polyphenols identified as intracellular protein kinase A inhibitors
verfasst von: Jan Øivind Moskaug
Grethe I. Borge
Anne M. Fagervoll
Ingvild Paur
Harald Carlsen
Rune Blomhoff
Publikationsdatum: 01.12.2008
Verlag: D. Steinkopff-Verlag
Erschienen in: European Journal of Nutrition / Ausgabe 8/2008
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-008-0749-0

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Abstract

Background

Aims of study

Methods

Results

Conclusion

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