Luteolin protects HUVECs from TNF-α-induced oxidative stress and inflammation via its effects on the Nox4/ROS-NF-κB and MAPK pathways.

Abstract

AIM:

Inflammation and oxidative stress are now recognized to be two important contributing factors to the development of atherosclerosis(AS). NADPH oxidase-4 (Nox4)-derived reactive oxygen species(ROS), NF-κB and MAPK play crucial roles in these processes. Luteolin, a flavone rich in many plants, can interrupt the molecular expression and inhibit the progression of inflammation and oxidative stress. The present study was designed to test whether luteolin inhibits TNF-α-induced inflammation and oxidative stress in human umbilical vein endothelial cells(HUVECs) and identify some of the mechanisms underlying these effects.

METHODS:

HUVECs were treated with luteolin in the presence/absence of TNF-α. The mechanism of luteolin against TNF-α-induced cell injury was evaluated using Western blotting, real-time RT-PCR and flow cytometry analyses.

RESULTS:

Luteolin suppressed the TNF-α-activated ROS generation, as well as the Nox4, p22phox, and ICAM-1 and VCAM-1 expression. Luteolin also enhanced the Bcl-2 and reduced caspase-3, -9 expression in the TNF-α-treated HUVECs. Finally, luteolin inhibited the TNF-α-induced transcriptional activity of NF-κB and p38 in addition to ERK1/2 phosphorylation. The inhibitors and siRNA of Nox4 and NF-κB not only reduced ROS generation, p38, ERK1/2 phosphorylation and the ICAM-1 and VCAM-1 expression, but also enhanced Bcl-2 expression. The inhibitor of p38 had the same effect on the expression of ICAM-1, VCAM-1 and Bcl-2, while the inhibitor of ERK1/2 increased the Bcl-2 expression rather than reducing the ICAM-1 and VCAM-1 expression.

CONCLUSIONS:

Luteolin attenuates TNF-α-induced oxidative stress and inflammation via its effects on the Nox4/ROS-NF-κB and MAPK pathways. These results suggest that luteolin may provide a beneficial effect in treating vascular diseases associated with oxidative stress and inflammation.

• Authors: Fan Xia, Changyuan Wang, Yue Jin, Qi Liu, Qiang Meng, Kexin Liu, Huijun Sun
• Journal: Journal of atherosclerosis and thrombosis (J Atheroscler Thromb) Vol. 21 Issue 8 Pg. 768-83 ( 2014) ISSN: 1880-3873 [Electronic] Japan
• PMID: 24621786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• RNA, Messenger
• RNA, Small Interfering
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• NADPH Oxidase 4
• NADPH Oxidases
• NOX4 protein, human
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• Luteolin

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Cell Adhesion (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Inflammation (metabolism, pathology, prevention & control)
• Luteolin (pharmacology)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• NADPH Oxidase 4
• NADPH Oxidases (antagonists & inhibitors, genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Reactive Oxygen Species (metabolism)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (pharmacology)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)