Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa B activation in Leptin-induced Human Umbilical Vein Endothelial Cells (HUVECs)

Abstract

BackgroundHigh concentrations of plasma leptin and the release of pro-inflammatory cytokines in leptin-resistance in obesity have been reported to trigger endothelial dysfunction. The objective of this study was to elucidate the role of quercetin in modulating leptin-induced inflammation as assessed by the levels of Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF-alpha secretion in umbilical vein endothelial cells (HUVECs) in vitro.FindingsHUVECs were exposed to either control levels (0 ng/ml) or 500 ng/mL leptin (L) for 48 hours, followed by control or 125 uM quercetin (Q) for another 6 h. The experimental groups were as follows: L0Q0, L0Q125, L500Q0, L500Q125. The presence of the short chain leptin receptor isoform Ob-Ra in HUVECs was determined by Western blot and immunocytochemistry analyses. Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF-alpha secretion were quantified by ELISA, and NF-kappa B activationby immunofluorescence staining. Our results showed that Ob-Ra expression, ERK1/2 phosphorylation and NF-kappa B activation increased significantly after 500 ng/mL leptin exposure (1.8x, 1.5x, 6.2x for Ob-Ra, ERK1/2 and NF-kappa B, respectively), but were reduced by addition of 125 uM quercetin (0.7x, 0.3x and 0.4x for Ob-Ra, ERK1/2 and NF-kappa B, respectively), and that quercetin could also partially suppress leptin-induced TNF-alpha secretion (3.8x) by 0.8x.ConclusionExposure of HUVECs to leptin up-regulated Ob-Ra expression and elevated ERK1/2 phosphorylation and NFkB activation, and increased TNF-alpha secretion. These effects strongly suppressed by quercetin, with the exception of TNF-alpha which was partially suppressed. The findings might be of clinical significance, as endothelial dysfunction that could lead to cardiovascular disease is preventable, and quercetin is a natural compound found in various plants and fruits.

The Essential Role of Pin1 via NF-κB Signaling in Vascular Inflammation and Atherosclerosis in ApoE−/− Mice

“…It has been reported that Pin1 can regulate the activities of ERK, JNK, and NF-κB [3,9,12,13]. Meanwhile, these signal pathways play important roles in endothelial dysfunction [2,9,14,15]. However, it is yet unknown which is involved in Pin1-regulated vascular inflammation and atherosclerosis in ApoE −/− mice.…”

Role of quercetin as an alternative for obesity treatment: You are what you eat!

“…In many cases, the protective effects of this compound have been linked to its anti-inflammatory and/or antioxidant properties. In HUVEC cells, the negative effect of leptin addition on the expression of short chain leptin receptor isoform (Ob-Ra), ERK1/2 phosphorylation and NF-κ B activation was reduced by the addition of 125 µM quercetin, suggesting that the suppression of inflammation by quercetin may be of clinical relevance in the prevention of the diseases induced by leptin-resistant in obesity (Indra, Karyono, Ratnawati, & Malik, 2013). A similar anti-inflammatory effect of quercetin has been shown in macrophages, which infiltrate white adipose tissue, contributing to the chronic inflammation observed in obese subjects.…”

Modulation of leptin resistance by food compounds

“…It is also important to highlight the findings obtained by Indra et al . , in which the administration of quercetin, a flavonol found in many fruits, produced an overexpression of LepRa in HUVEC cells. This finding is very important due to the involvement of this receptor in the transport of leptin through the BBB.…”