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The flavonoid luteolin induces nitric oxide production and arterial relaxation

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Luteolin, a flavone present in many foods and medicinal plants, may have beneficial effects on various human chronic diseases. In the present study, we investigated the hypothesis that luteolin can directly act on vascular endothelial cells (ECs), leading to nitric oxide (NO) production and subsequent vascular relaxation.

Methods

Rat aortic rings were mounted in organ bath. Luteolin was added cumulatively, and vessel relaxation of rat aortic rings precontracted with phenylephrine (PE) or potassium was recorded. Endothelial nitric oxide synthase (eNOS) phosphorylation at Ser1177 and NO production from aortic rings and primary human aortic endothelial cells (HAECs) exposed to luteolin were measured by using Western blot and fluorometric assay, respectively.

Results

Luteolin dose-dependently (10–100 μmol/L) elicited relaxation of PE- or potassium-contracted aortic rings. The vasorelaxation effect of luteolin was attenuated by the eNOS inhibitor, N-nitro-l-arginine methyl ester, suggesting that this luteolin action is at least partially mediated by activating eNOS activity. We further found that luteolin dose-dependently (10–100 μmol/L) increased eNOS phosphorylation at Ser1177 (up to 1.9-fold) in isolated rat rings. Consistently, exposure of HAECs to luteolin also increased eNOS phosphorylation and NO production.

Conclusions

Luteolin may be a vascular protective agent by directly acting on vascular ECs to stimulate NO-dependent vascular dilatation.

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Abbreviations

Ach:

Acetylcholine

α1-AR:

α (1) Adrenergic receptor

[Ca2+]i:

Cytosolic Ca2+ levels

cGMP:

Cyclic guanosine monophosphate

DMSO:

Dimethyl sulfoxide

EGM2:

Endothelial growth supplements 2

eNOS:

Endothelial nitric oxide synthase

FBS:

Fetal bovine serum

HAECs:

Human aortic endothelial cells

HBSS:

Hank’s balanced salt solution

KH:

Krebs–Henseleit

L-NAME:

N-nitro-l-arginine methyl ester

NO:

Nitric oxide

PE:

Phenylephrine

PKA:

Protein kinase A

SMCs:

Smooth muscle cells

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Acknowledgments

We would like to thank the financial supports from the National Center for Complementary and Alternative Medicine of National Institute of Health (1R21AT004694 and 1R21AT002739 to D. L) and American Diabetes Association (1-08-JF-30 to D. Liu).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Human Nutrition, Foods and Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA, 24061, USA

    Hongwei Si & Dongmin Liu

  2. Department of Family and Consumer Sciences, College of Agriculture, Human and Natural Sciences, Tennessee State University, Nashville, TN, 37209, USA

    Hongwei Si

  3. Edward Via College of Osteopathic Medicine, Virginia Campus, Blacksburg, VA, 24060, USA

    Richard P. Wyeth

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  1. Hongwei Si
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Correspondence to Dongmin Liu.

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Si, H., Wyeth, R.P. & Liu, D. The flavonoid luteolin induces nitric oxide production and arterial relaxation. Eur J Nutr 53, 269–275 (2014). https://doi.org/10.1007/s00394-013-0525-7

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  • DOI: https://doi.org/10.1007/s00394-013-0525-7

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