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

BMC Research Notes

Safarina G Malik²  Retty Ratnawati¹  Satuman Karyono¹  Mochamad Rasjad Indra¹ 

[1]Department of Physiology, Faculty of Medicine, Brawijaya University, Jl. Veteran, Malang 65145, East Java, Indonesia

[2]Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia

关键词: HUVECs;    TNFα;    NFκB;    ERK1/2;    Ob-Ra;    Quercetin;    Leptin;   

Others  :  1142155
DOI  :  10.1186/1756-0500-6-275

 received in 2012-01-06, accepted in 2013-06-24,  发布年份 2013

【 摘 要 】

Background

High 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.

Findings

HUVECs 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.

Conclusion

Exposure 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.

【 授权许可】

   
2013 Indra et al.; licensee BioMed Central Ltd.

【 图 表 】

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