Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway.

Abstract

Vascular inflammation plays a significant role in the pathogenesis of atherosclerosis. Luteolin, a naturally occurring flavonoid present in many medicinal plants and some commonly consumed fruits and vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of luteolin at physiological concentrations remain unclear. Here, we report that luteolin as low as 0.5 μM significantly inhibited tumor necrosis factor (TNF)-α-induced adhesion of monocytes to human EA.hy 926 endothelial cells, a key event in triggering vascular inflammation. Luteolin potently suppressed TNF-α-induced expression of the chemokine monocyte chemotactic protein-1 (MCP-1) and adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), key mediators involved in enhancing endothelial cell-monocyte interaction. Furthermore, luteolin inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, IκBα degradation, expression of IκB kinase β and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that luteolin can inhibit inflammation by suppressing NF-κB signaling. In an animal study, C57BL/6 mice were fed a diet containing 0% or 0.6% luteolin for 3 weeks, and luteolin supplementation greatly suppressed TNF-α-induced increase in circulating levels of MCP-1/JE, CXCL1/KC and sICAM-1 in C57BL/6 mice. Consistently, dietary intake of luteolin significantly reduced TNF-α-stimulated adhesion of monocytes to aortic endothelial cells ex vivo. Histology shows that luteolin treatment prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization as shown by Verhoeff-Van Gieson staining. Immunohistochemistry studies further show that luteolin treatment also reduced VCAM-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, luteolin protects against TNF-α-induced vascular inflammation in both in vitro and in vivo models. This anti-inflammatory effect of luteolin may be mediated via inhibition of the NF-κB-mediated pathway.

• Authors: Zhenquan Jia, Palanisamy Nallasamy, Dongmin Liu, Halley Shah, Jason Z Li, Rojin Chitrakar, Hongwei Si, John McCormick, Hong Zhu, Wei Zhen, Yunbo Li
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 26 Issue 3 Pg. 293-302 (Mar 2015) ISSN: 1873-4847 [Electronic] United States
• PMID: 25577468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• CCL2 protein, human
• Chemokine CCL2
• I-kappa B Proteins
• ICAM1 protein, human
• NF-kappa B
• NFKBIA protein, human
• Nfkbia protein, mouse
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• NF-KappaB Inhibitor alpha
• Luteolin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (metabolism, therapeutic use)
• Aorta (immunology, metabolism, pathology)
• Cell Adhesion
• Cell Line
• Cells, Cultured
• Chemokine CCL2 (antagonists & inhibitors, blood, genetics, metabolism)
• Dietary Supplements
• Endothelium, Vascular (cytology, immunology, metabolism, pathology)
• Human Umbilical Vein Endothelial Cells (cytology)
• I-kappa B Proteins (antagonists & inhibitors, metabolism)
• Intercellular Adhesion Molecule-1 (blood, chemistry, metabolism)
• Luteolin (metabolism, therapeutic use)
• Macrophages (immunology, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Monocytes (immunology, metabolism, pathology)
• NF-KappaB Inhibitor alpha
• NF-kappa B (antagonists & inhibitors, metabolism)
• Random Allocation
• Signal Transduction
• Specific Pathogen-Free Organisms
• Vascular Cell Adhesion Molecule-1 (chemistry, metabolism)
• Vasculitis (diet therapy, immunology, metabolism, pathology)