Naringin inhibits TNF-α induced oxidative stress and inflammatory response in HUVECs via Nox4/NF-κ B and PI3K/Akt pathways.
In the development of atherosclerosis, naringin has exhibited potential protective effects. However, the specific mechanisms are not clearly understood. The aim of this trial was to determine the anti-oxidative and anti-inflammatory effects of naringin and uncover the mechanisms in Tumor Necrosis Factor-alpha (TNF-α) induced Human Umbilical Vein Endothelial Cells (HUVECs). Reactive Oxygen Species (ROS) were measured by flow cytometry assay. The levels of NADPH oxidase 4 (Nox4), p22(phox), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) over-expressions were measured by qRT-PCR and Western blotting analyses. Activation of Phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Nuclear Factor-κB (NF-κB) was evaluated by Western blotting. Naringin inhibited ROS production as well as over-expression levels of Nox4, p22(phox) induced by TNF-α. Naringin inhibited TNF-α induced mRNA and protein over-expressions of ICAM-1 and VCAM-1. Naringin also suppressed activation of NF-κB and PI3K/Akt signaling pathways. These results indicated the preventive effects of naringin on HUVECs injury caused by oxidative stress and inflammation response and the effects might be obtained via inhibition of Nox4 and NF-κB pathways as well as activation of PI3K/Akt pathway. Naringin may be useful in preventing endothelial dysfunction, therefore to ameliorate the development of atherosclerosis.
Wenshuang
W
Li
Changyuan
C
Wang
Jinyong
J
Peng
Jing
J
Liang
Yue
Y
Jin
Qi
Q
Liu
Qiang
Q
Meng
Kexin
K
Liu
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044, China. sunhuijun@dlmedu.edu.cn.
Huijun
H
Sun
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D044950:Flavanones / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D044950:Flavanones; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C086986:CYBA protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C005274:naringin