The flavonoid luteolin induces nitric oxide production and arterial relaxation.

The flavonoid luteolin induces nitric oxide production and arterial relaxation.
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DOI:
10.1007/s00394-013-0525-7
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发表时间:
2014-02
影响因子:
5
通讯作者:
Liu D
Liu D
中科院分区:
医学2区
文献类型:
--
作者:
Si H;Wyeth RP;Liu D

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木犀草素是一种存在于许多食品和药用植物中的黄酮类化合物,可能对人类各种慢性病有有益的作用。在目前的研究中,我们研究了木犀草素可以直接作用于血管内皮细胞,导致一氧化氮(NO)的产生和随后的血管松弛的假设。将大鼠主动脉环固定于脏器浴中。累积加入木犀草素,记录苯肾上腺素(PE)或钾预先收缩的大鼠主动脉环的血管松弛。用Western印迹和荧光法分别检测木犀草素作用下主动脉环和原代培养的人主动脉内皮细胞(HAECs)Ser1177位内皮型一氧化氮合酶(ENOS)的磷酸化和NO的产生。木犀草素可剂量依赖性地(10-100mol.mo1/L)引起PE或钾收缩的主动脉环松弛。木犀草素的血管舒缩作用可被eNOS抑制剂N-硝基-L-精氨酸甲酯减弱,提示木犀草素的这一作用至少部分是通过激活eNOS活性来实现的。我们进一步发现,木犀草素(10-100Mol/L)可剂量依赖性地增加大鼠离体环1177位μ的eNOS磷酸化水平(最高达1.9倍)。一贯地,木犀草素对HAECs的暴露也增加了eNOS的磷酸化和NO的产生。木犀草素可能是一种血管保护剂,直接作用于血管内皮细胞,刺激NO依赖的血管扩张。
Luteolin, a flavone present in many foods and medicinal plants, may have beneficial effects on various human chronic diseases. In the present study, we investigated the hypothesis that luteolin can directly act on vascular endothelial cells (ECs), leading to nitric oxide (NO) production and subsequent vascular relaxation. Rat aortic rings were mounted in organ bath. Luteolin was added cumulatively and vessel relaxation of rat aortic rings precontracted with phenylephrine (PE) or potassium was recorded. Endothelial nitric oxide synthase (eNOS) phosphorylation at Ser1177 and NO production from aortic rings and primary human aortic endothelial cells (HAECs) exposed to luteolin were measured by using Western blot and fluorometric assay, respectively. Luteolin dose-dependently (10-100 μmol/L) elicited relaxation of PE- or potassium-contracted aortic rings. The vasorelaxation effect of luteolin was attenuated by the eNOS inhibitor, N-nitro-L-arginine methyl ester, suggesting that this luteolin action is at least partially mediated by activating eNOS activity. We further found that luteolin dose-dependently (10-100 μmol/L) increased eNOS phosphorylation at Ser1177 (up to 1.9 fold) in isolated rat rings. Consistently, exposure of HAECs to luteolin also increased eNOS phosphorylation and NO production. Luteolin may be a vascular protective agent by directly acting on vascular ECs to stimulate NO-dependent vascular dilatation.
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