PMID- 31195734
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20200309
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 9
IP  - 6
DP  - 2019 Jun 5
TI  - Screening of Inhibitory Effects of Polyphenols on Akt-Phosphorylation in 
      Endothelial Cells and Determination of Structure-Activity Features.
LID - 10.3390/biom9060219 [doi]
LID - 219
AB  - 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 44 
      polyphenols (10 microM) 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.
FAU - Dirimanov, Stoyan
AU  - Dirimanov S
AD  - Institut fur Pharmazie und Lebensmittelchemie, Universitat Wurzburg, Am Hubland, 
      97074 Wurzburg, Germany. stoyan.dirimanov@uni-wuerzburg.de.
FAU - Hogger, Petra
AU  - Hogger P
AD  - Institut fur Pharmazie und Lebensmittelchemie, Universitat Wurzburg, Am Hubland, 
      97074 Wurzburg, Germany. petra.hoegger@uni-wuerzburg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190605
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Polyphenols)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Cell Line
MH  - Drug Evaluation, Preclinical
MH  - Endothelial Cells/*drug effects/*metabolism
MH  - Humans
MH  - Phosphorylation/drug effects
MH  - Polyphenols/*chemistry/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Structure-Activity Relationship
PMC - PMC6627700
OTO - NOTNLM
OT  - Akt/PKB
OT  - diabetes
OT  - endothelium
OT  - in vitro
OT  - polyphenols
OT  - screening
OT  - structure-activity relationships
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2019/06/15 06:00
MHDA- 2020/02/26 06:00
PMCR- 2019/06/01
CRDT- 2019/06/15 06:00
PHST- 2019/05/04 00:00 [received]
PHST- 2019/06/03 00:00 [revised]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/06/15 06:00 [entrez]
PHST- 2019/06/15 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/06/01 00:00 [pmc-release]
AID - biom9060219 [pii]
AID - biomolecules-09-00219 [pii]
AID - 10.3390/biom9060219 [doi]
PST - epublish
SO  - Biomolecules. 2019 Jun 5;9(6):219. doi: 10.3390/biom9060219.