An aqueous pomegranate peel extract inhibits neutrophil myeloperoxidase in vitro and attenuates lung inflammation in mice
An aqueous pomegranate peel extract inhibits neutrophil myeloperoxidase in vitro and attenuates lung inflammation in mice
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DOI：
10.1016/j.fct.2011.02.024
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发表时间：
2011-06-01
影响因子：
4.3
通讯作者：
El-Benna, Jamel
中科院分区：
文献类型：
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作者：
Bachoual, Rafik;Talmoudi, Wifak;El-Benna, Jamel
石榴皮水提取物 (PGE) 广泛用于治疗炎症、溃疡和感染等疾病，但其药理靶点尚不清楚。在这项研究中，我们研究了 PGE 对体外人中性粒细胞活性氧 (ROS) 产生的影响以及对 LPS 诱导的小鼠体内肺部炎症的影响。分离中性粒细胞并通过鲁米诺放大化学发光测量ROS的产生。通过细胞色素c还原测定检测超氧阴离子的产生。采用DCFH荧光法检测H(2)O(2)。髓过氧化物酶（MPO）活性通过四甲基联苯胺氧化法测定。通过LPS滴注诱导小鼠肺部炎症。 PGE 以浓度依赖性方式抑制静息中性粒细胞和 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸 (fMLF) 或佛波醇肉豆蔻酸酯 (PMA) 刺激的中性粒细胞的鲁米诺放大化学发光。 PGE 对超氧阴离子的产生没有影响，表明它不会直接抑制 NADPH 氧化酶活性或激活途径，或清除超氧阴离子。 PGE在体外不清除H(2)O(2)，而是直接抑制髓过氧化物酶活性。体内研究表明，PGE 还能减轻 LPS 诱导的小鼠肺部炎症。因此，这项研究表明，PGE 可抑制中性粒细胞 MPO 活性并减轻 LPS 诱导的小鼠肺部炎症。 PGE 对 MPO 活性的抑制可以解释其抗炎作用。 (C) 2011 Elsevier Ltd. 保留所有权利。
Punica granatum peel aqueous extract (PGE) is widely used to treat disorders such as inflammation, ulcers and infections, but its pharmacological target is not known. In this study we investigated the effect of PGE on human neutrophil reactive oxygen species (ROS) production in vitro and on LPS-induced lung inflammation in vivo in mice. Neutrophils were isolated and ROS generation was measured by luminol-amplified chemiluminescence. Superoxide anion generation was detected by the cytochrome c reduction assay. H(2)O(2) was detected by DCFH fluorescence assay. Myeloperoxidase (MPO) activity was measured by the tetramethyl benzidine oxidation method. Lung inflammation was induced in mice by LPS instillation. PGE inhibited luminol-amplified chemiluminescence of resting neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLF)- or phorbol myristate acetate (PMA)-stimulated neutrophils, in a concentration-dependent manner. PGE had no effect on superoxide anion generation, suggesting that it does not directly inhibit NADPH oxidase activity or activation pathways, or scavenge superoxide anions. PGE did not scavenge H(2)O(2) but directly inhibited myeloperoxidase activity in vitro. In vivo studies showed that PGE also attenuated LPS-induced lung inflammation in mice. So this study reveals that PGE inhibits neutrophil MPO activity and attenuates LPS-induced lung inflammation in mice. Inhibition of MPO activity by PGE could explain its anti-inflammatory action. (C) 2011 Elsevier Ltd. All rights reserved.