Quercetin inhibits TNF-α induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro

Medicine (Baltimore). 2020 Sep 18;99(38):e22241. doi: 10.1097/MD.0000000000022241.

Abstract

Background: Quercetin, a major flavonol, wildly exists in plantage, which has been reported to have an anti-apoptosis and anti-inflammation effects on vascular endothelial cells, but its underlying molecular mechanisms remain unclear.

Objective: The aim of this study was to investigate the mechanisms of how quercetin inhibits tumor necrosis factor alpha (TNF-α) induced human umbilical vein endothelial cells (HUVECs) apoptosis and inflammation.

Methods and results: HUVECs were preconditioned with quercetin for 18 hours, and subsequently treated with TNF-α for 6 hours to induce apoptosis. The expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, β-actin mRNA was then detected by RT-PCR. Flow cytometry was used to estimate the apoptosis rates, and the expression of activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) was measured by Western blot. TNF-α induced elevated apoptosis rates and upregulation of VCAM-1, ICAM-1, and E-selectin were meaningfully reduced in HUVECs by pretreatment with quercetin. In addition, quercetin also inhibited the activation of AP-1and NF-κB.

Conclusion: Results indicate that quercetin could suppress TNF-α induced apoptosis and inflammation by blocking NF-κB and AP-1 signaling pathway in HUVECs, which might be one of the underlying mechanisms in treatment of coronary heart disease.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects*
  • Down-Regulation
  • E-Selectin / metabolism
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Intercellular Adhesion Molecule-1 / metabolism
  • NF-kappa B / metabolism*
  • Quercetin / pharmacology*
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • E-Selectin
  • ICAM1 protein, human
  • NF-kappa B
  • SELE protein, human
  • TNF protein, human
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Quercetin