Eriodictyol protects endothelial cells against oxidative stress-induced cell death through modulating ERK/Nrf2/ARE-dependent heme oxygenase-1 expression

Seung Eun Lee, Hana Yang, Gun Woo Son, Hye Rim Park, Cheung Seog Park, Young Ho Jin, Yong Seek Park

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)14526-14539
Number of pages14
JournalInternational journal of molecular sciences
Volume16
Issue number7
DOIs
StatePublished - Jun 26 2015

Bibliographical note

Publisher Copyright:
© 2015 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

  • Cell death
  • Endothelial cells
  • Eriodictyol
  • Flavonoid
  • Heme oxygenase-1
  • Oxidative stress

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