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Plant Foods for Human Nutrition

, Volume 70, Issue 3, pp 263–268 | Cite as

Pterostilbene, an Active Constituent of Blueberries, Stimulates Nitric Oxide Production via Activation of Endothelial Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells

  • Seong Hoon Park
  • Sun-Oh Jeong
  • Hun-Teag Chung
  • Hyun-Ock Pae
Original Paper

Abstract

Endothelial dysfunction, a key process in development of cardiovascular diseases, is largely due to reduced nitric oxide (NO) derived from endothelial NO synthase (eNOS). Resveratrol has been reported to stimulate NO production via estrogen receptor α (ERα) activation in endothelial cells. Here, we investigated whether two natural methylated analogs of resveratrol, pterostilbene (Pts) and trans-3,5,4’-trimethoxystilbene (TMS), similarly to resveratrol, could influence endothelial NO release in human umbilical vein endothelial cells (HUVECs). In HUVECs exposed to Pts or TMS, NO production and phosphorylation of eNOS, protein kinase B (Akt), and ERα were measured by using a fluorimetric NO assay kit and Western blot analysis, respectively. Dimethylated Pts, but not trimethylated TMS, stimulated dose-dependent NO production via eNOS phosphorylation. Pts also stimulated dose-dependent phosphorylation of Akt, but not of ERα. NO production and eNOS phosphorylation in response to Pts were significantly abolished by the phosphoinositide 3-kinase (PI3K)/Akt inhibitor LY294002, but not by the ERα antagonist ICI182780. Our results suggest that Pts, but not TMS, is capable of inducing eNOS phosphorylation and the subsequent NO release, presumably, by activating PI3K/Akt pathway. The potential efficacy of Pts, an active constituent of blueberries, may aid in the prevention of cardiovascular diseases characterized by endothelial dysfunction.

Keywords

Pterostilbene NO eNOS Endothelial cells Endothelial dysfunction 

Abbreviations

Akt

Protein kinase B

DMSO

Dimethyl sulfoxide

eNOS

Endothelial nitric oxide synthase

ERα

Estrogen receptor α

HBSS

Hank’s balanced salt solution

HRP

Horseradish peroxidase

HUVECs

Human umbilical vein endothelial cells

L-NAME

N G-Nitro-L-arginine methyl ester

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NO

Nitric oxide

PI3K

Phosphoinositide 3-kinase

Pts

Pterostilbene

TMS

trans-3,5,4’-Trimethoxystilbene

Notes

Acknowledgments

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) (no. 2012M3A9C3048686).

Conflict of interest

The authors declare no conflicting interests or financial disclosures.

Supplementary material

11130_2015_488_MOESM1_ESM.doc (72 kb)
ESM 1 (DOC 71 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Seong Hoon Park
    • 3
  • Sun-Oh Jeong
    • 2
  • Hun-Teag Chung
    • 2
  • Hyun-Ock Pae
    • 1
  1. 1.Department of Microbiology and ImmunologyWonkwang University School of MedicineIksanRepublic of Korea
  2. 2.Department of Biological ScienceUniversity of UlsanUlsanRepublic of Korea
  3. 3.Institute for Metabolic DiseaseWonkwang UniversityIksanRepublic of Korea

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