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Aqueous Cichorium intybus L. seed extract may protect against acute palmitate-induced impairment in cultured human umbilical vein endothelial cells by adjusting the Akt/eNOS pathway, ROS: NO ratio and ET-1 concentration

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Abstract

Background

Endothelial dysfunction, which is a vascular response to oxidative stress and inflammation, involves a cascade of downstream events that lead to decreased synthesis of insulin-mediated vasodilator nitric oxide (NO) and increased production of vasoconstrictor protein endothelin-1 (ET-1). NO, and ET-1 production by endothelial cells is regulated by phosphatidylinositol 3-kinase (PI3K)-Akt-eNOS axis and mitogen-activated protein kinase (MAPK) axis of the insulin signaling pathway, respectively.

Methods

After treating the human umbilical vein endothelial cells (HUVECs) with either palmitate complexed with bovine serum albumin (BSA) (abbreviated as PA) or the aqueous Cichorium intybus L. (chicory) seed extract (chicory seed extract, abbreviated as CSE) alone, and simultaneously together (PA + CSE), for 3, 12, and 24 h, we evaluated the capacity of CSE to reestablish the PA-induced imbalance between PI3K/Akt/eNOS and MAPK signaling pathways. The level of oxidative stress was determined by fluorimeter. Insulin-induced levels of NO and ET-1 were measured by Griess and ELISA methods, respectively. Western blotting was used to determine the extent of Akt and eNOS phosphorylation.

Results

Contrary to PA that caused an increase in the reactive oxygen species (ROS) levels and attenuated NO production, CSE readjusted the NO/ROS ratio within 12 h. CSE improved the metabolic arm of the insulin signaling pathway by up-regulating the insulin-stimulated phospho-eNOS Ser1177/total eNOS and phospho-Akt Thr308/total Akt ratios and decreased ET-1 levels.

Conclusions

CSE ameliorated the PA-induced endothelial dysfunction not only by its anti-ROS property but also by selectively enhancing the protective arm and diminishing the injurious arm of insulin signaling pathways.

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Abbreviations

Akt:

(Protein kinase B)

AMPK:

5' Adenosine Monophosphate-Activated Protein Kinase

BSA:

Bovine Serum Albumin

CSE:

Chicory Seed Extract (aqueous)

DMEM:

Dulbecco's Modified Eagle's Medium

eNOS:

Endothelial Nitric Oxide Synthase

ET-1:

Endothelin-1

FBS:

Fetal Bovine Serum

FFA:

Free Fatty Acids

HUVECs:

Human Umbilical Vein Endothelial Cells

HRP:

Horseradish Peroxidase

IKKβ:

Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Beta

iNOS:

Inducible Nitric Oxide Synthase

INSR:

Insulin Receptor

IR:

Insulin Resistance

MTT:

3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl-2H-Tetrazolium Bromide

MAPK:

Mitogen-Activated Protein Kinase

PES:

Polyethersulfone

NO:

Nitric Oxide

NF-κB:

Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells

PA:

an abbreviation for palmitate-BSA

PI3K:

Phosphatidylinositol 3-Kinase

PKA:

Protein Kinase A

ROS:

Reactive Oxygen Species

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Acknowledgments

The authors would like to thank Mr. Ali-Akbar Hasseli of the Institute of Biochemistry and Biophysics (IBB) for his help with fluorimeter and fluorescence microscope. This article is the product of the MSc thesis of the first author.

Funding

This work was financially supported by Tehran University of Medical Sciences and Health Services under Grant No. 95–02–30-32269.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Raziyeh Abdolahipour, Azin Nowrouzi & Samin Ardalani

  2. Institue of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    Masoumeh Babaei Khalili

  3. Department of Community & Preventive Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Alipasha Meysamie

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  1. Raziyeh Abdolahipour
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  2. Azin Nowrouzi
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Contributions

RA conceptualized the idea and performed the experiments; AN conceptualized the idea and wrote the paper; MBK provided technical assistance; AM assisted with statistical analysis; SA helped drafting the manuscript.

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Correspondence to Azin Nowrouzi.

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Abdolahipour, R., Nowrouzi, A., Khalili, M.B. et al. Aqueous Cichorium intybus L. seed extract may protect against acute palmitate-induced impairment in cultured human umbilical vein endothelial cells by adjusting the Akt/eNOS pathway, ROS: NO ratio and ET-1 concentration. J Diabetes Metab Disord 19, 1045–1059 (2020). https://doi.org/10.1007/s40200-020-00603-3

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