Kaempferol inhibits the production of ROS to modulate OPN-αvβ3 integrin pathway in HUVECs

J Physiol Biochem. 2016 Jun;72(2):303-13. doi: 10.1007/s13105-016-0479-3. Epub 2016 Mar 21.

Abstract

In the present study, we tested the hypothesis that aldosterone regulates osteopontin (OPN)-related signaling pathways to promote nuclear factor κB (NF-κB) activation in primary human umbilical vein endothelial cells (HUVECs) and that kaempferol, a flavonoid compound, blocks those changes. Aldosterone induced productions of reactive oxygen species (ROS), OPN, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) and expression of nicotinamide adenine dinucleotide phosphate-oxidase 4 (Nox4), NF-κB, OPN, alphavbeta3 (αvβ3) integrin, and inhibitor of NF-κB alpha phosphorylation (P-IκBα) in HUVEC. HUVECs were pretreated with kaempferol (0, 1, 3, or 10 μM) for 1 h and exposed to aldosterone (10(-6) M) for 24 h. Kaempferol reduced ROS, OPN, NF-κB, IL-6, and TNF-α levels; Nox4, αvβ3 integrin; and P-IκBα expressions. The effect of aldosterone was also abrogated by spironolactone (10(-6) M). In addition, vitamin C (20 mmol/L) reduced ROS production. Vitamin C and LM609 (10 μg/mL) treatment decreased expressions of OPN, αvβ3 integrin, and NF-κB (P < 0.05 or P < 0.01). The present results suggest that kaempferol may modulate OPN-αvβ3 integrin pathway to inhibit NF-κB activation in HUVECs.

Keywords: Aldosterone; Human umbilical vein endothelial cells; Kaempferol; Nuclear factor κB; Osteopontin; αvβ3 Integrin.

MeSH terms

  • Aldosterone / chemistry
  • Aldosterone / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antibodies, Monoclonal / pharmacology
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology
  • Cells, Cultured
  • Down-Regulation / drug effects*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Human Umbilical Vein Endothelial Cells / cytology
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Integrin alphaV / chemistry
  • Integrin alphaV / metabolism
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin beta3 / chemistry
  • Integrin beta3 / metabolism
  • Kaempferols / pharmacology*
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Osteopontin / antagonists & inhibitors
  • Osteopontin / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Spironolactone / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Antioxidants
  • ITGB3 protein, human
  • Inflammation Mediators
  • Integrin alphaV
  • Integrin alphaVbeta3
  • Integrin beta3
  • Kaempferols
  • LM609 monoclonal antibody
  • Mineralocorticoid Receptor Antagonists
  • NF-kappa B
  • Reactive Oxygen Species
  • SPP1 protein, human
  • Osteopontin
  • Spironolactone
  • Aldosterone
  • kaempferol
  • Ascorbic Acid