Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway.
Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway.
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DOI：
10.1016/j.jnutbio.2014.11.008
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Jia Z;Nallasamy P;Liu D;Shah H;Li JZ;Chitrakar R;Si H;McCormick J;Zhu H;Zhen W;Li Y
血管炎症在动脉粥样硬化的发病机制中起重要作用。木犀草素是一种天然存在的类黄酮，存在于许多药用植物以及一些常见的水果和蔬菜中，因其在体外改善血管功能的潜力而受到广泛关注。然而，木犀草素在生理浓度下的体内作用和分子机制尚不清楚。在这里，我们报道低至0.5 μM的木犀草素显著抑制TNF-α-诱导的单核细胞与人内皮细胞的粘附，这是引发血管炎症的关键事件。木犀草素能有效抑制TNF-α诱导的趋化因子单核细胞趋化蛋白-1 （MCP-1）和粘附分子ICAM-1和VCAM-1的表达，这是促进内皮细胞-单核细胞相互作用的关键介质。此外，木犀草素抑制TNF-α-诱导的内皮细胞NF-κB转录活性、i -κB α降解、i -κB激酶β （IKKß）表达以及随后的NF-κB p65核易位，提示木犀草素可以通过抑制NF-κB信号传导来抑制炎症。在动物实验中，给C57BL/6小鼠饲喂含有0%或0.6%木犀草素的日粮3周，添加木犀草素可显著抑制TNF-α-诱导的C57BL/6小鼠MCP-1/JE、CXCL1/KC和sICAM-1循环水平的升高。同样，饮食中摄入木犀草素可显著降低TNF-α刺激的单核细胞对主动脉内皮细胞的体外粘附。verhoefff -van Gieson染色显示木犀草素处理可阻止主动脉内膜内皮细胞的破裂，并保留弹性蛋白纤维的精细组织。免疫组织化学进一步研究表明，木犀草素处理还能降低TNF-α-处理小鼠主动脉中VCAM-1和单核细胞来源的f4 /80阳性巨噬细胞。综上所述，木犀草素对体外和体内模型中TNF-α-诱导的血管炎症具有保护作用。木犀草素的这种抗炎作用可能是通过抑制NF-κ b介导的途径介导的。
Vascular inflammation plays a significant role in the pathogenesis of atherosclerosis. Luteolin, a naturally-occurring flavanoid, present in many medicinal plants as well as in 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 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 ICAM-1 and VCAM-1, key mediators involved in enhancing endothelial cell-monocyte interaction. Furthermore, luteolin inhibited TNF-α-induced NF-κB transcriptional activity, IκBα degradation, expression of IκB kinase ß (IKKß), 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 three weeks and luteolin supplementation greatly suppressed TNF-α-induced increases 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.
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影响因子：
56.9
作者：
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