Screening of inhibitory effects of polyphenols on Akt-phosphorylation in endothelial cells and determination of structure-activity features
Please always quote using this URN: urn:nbn:de:bvb:20-opus-197333
- Polyphenols exert beneficial effects in type 2 diabetes mellitus (T2DM). However, their mechanism of action remains largely unknown. Endothelial Akt-kinase plays a key role in the pathogenesis of cardiovascular complications in T2DM and therefore the modulation of its activity is of interest. This work aimed to characterize effects of structurally different polyphenols on Akt-phosphorylation (pAkt) in endothelial cells (Ea.hy926) and to describe structure-activity features. A comprehensive screening via ELISA quantified the effects of 44Polyphenols exert beneficial effects in type 2 diabetes mellitus (T2DM). However, their mechanism of action remains largely unknown. Endothelial Akt-kinase plays a key role in the pathogenesis of cardiovascular complications in T2DM and therefore the modulation of its activity is of interest. This work aimed to characterize effects of structurally different polyphenols on Akt-phosphorylation (pAkt) in endothelial cells (Ea.hy926) and to describe structure-activity features. A comprehensive screening via ELISA quantified the effects of 44 polyphenols (10 µM) on pAkt Ser473. The most pronounced inhibitors were luteolin (44 ± 18%), quercetin (36 ± 8%), urolithin A (35 ± 12%), apigenin, fisetin, and resveratrol; (p < 0.01). The results were confirmed by Western blotting and complemented with corresponding experiments in HUVEC cells. A strong positive and statistically significant correlation between the mean inhibitory effects of the tested polyphenols on both Akt-residues Ser473 and Thr308 (r = 0.9478, p = 0.0003) was determined by immunoblotting. Interestingly, the structural characteristics favoring pAkt inhibition partially differed from structural features enhancing the compounds’ antioxidant activity. The present study is the first to quantitatively compare the influence of polyphenols from nine different structural subclasses on pAkt in endothelial cells. These effects might be advantageous in certain T2DM-complications involving over-activation of the Akt-pathway. The suggested molecular mode of action of polyphenols involving Akt-inhibition contributes to understanding their effects on the cellular level.…
Author: | Stoyan Dirimanov, Petra Högger |
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URN: | urn:nbn:de:bvb:20-opus-197333 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie |
Language: | English |
Parent Title (English): | Biomolecules |
ISSN: | 2218-273X |
Year of Completion: | 2019 |
Volume: | 9 |
Issue: | 6 |
Pagenumber: | 219 |
Source: | Biomolecules 2019, 9(6), 219; https://doi.org/10.3390/biom9060219 |
DOI: | https://doi.org/10.3390/biom9060219 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Tag: | Akt/PKB; diabetes; endothelium; in vitro; polyphenols; screening; structure-activity relationships |
Release Date: | 2020/03/03 |
Date of first Publication: | 2019/06/05 |
Open-Access-Publikationsfonds / Förderzeitraum 2019 | |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |