The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production
The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production
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DOI：
10.1016/s0014-2999(03)02121-6
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发表时间：
2003-08-15
影响因子：
5
通讯作者：
Tsai, SK
中科院分区：
文献类型：
--
作者：
Liou, KT;Shen, YC;Tsai, SK
中性粒细胞产生的活性氧参与了局灶性脑缺血/再灌注损伤的发病机制，并发出炎症反应信号。我们以前已经表明，和厚朴，从厚朴中提取的活性成分，具有保护作用，对大鼠局灶性脑缺血/再灌注损伤，包括减少中性粒细胞产生活性氧。为了阐明和厚朴酚抗氧化作用的潜在机制，在存在或不存在和厚朴酚的情况下，用佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）或N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）激活从大鼠分离的外周中性粒细胞。在本研究中，我们发现和厚朴酚通过三种不同的机制抑制PMA或fMLP诱导的中性粒细胞活性氧的产生：（1）和厚朴酚使中性粒细胞中产生活性氧的主要酶-NADPH氧化酶的活性降低40%，而不干扰其蛋白激酶C（PKC）依赖的组装;（2）中性粒细胞中产生活性氧的另外两种重要酶，即，髓过氧化物酶和环氧合酶也分别被和厚朴酚抑制20%和70%;（3）和厚朴酚增强谷胱甘肽（GSH）过氧化物酶活性30%，谷胱甘肽是一种触发过氧化氢（H2 O2）代谢的酶。这些数据表明，和厚朴酚，作为一个有效的活性氧抑制剂/清除剂，可以实现其局灶性脑缺血/再灌注损伤的保护作用，通过调节酶系统的活性氧的生产或代谢，包括NADPH氧化酶，髓过氧化物酶，环氧合酶，谷胱甘肽过氧化物酶在中性粒细胞。
Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia/reperfusion injury and signal the inflammatory response. We have previously shown that honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s) of the antioxidative effect of honokiol, peripheral neutrophils isolated from rats were activated with phorbol-12-myristate-13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence or absence of honokiol. In this study, we found that honokiol inhibited PMA- or fMLP-induced reactive oxygen species production by neutrophils by three distinct mechanisms: (1) honokiol diminished the activity of assembled-NADPH oxidase, a major reactive oxygen species producing enzyme in neutrophils by 40% without interfering with its protein kinase C (PKC)-dependent assembly; (2) two other important enzymes for reactive oxygen species generation in neutrophils, i.e., myeloperoxidase and cyclooxygenase, were also inhibited by honokiol by 20% and 70%, respectively; and (3) honokiol enhanced glutathione (GSH) peroxidase activity by 30%, an enzyme that triggers the metabolism of hydrogen peroxide (H2O2). These data suggested that honokiol, acting as a potent reactive oxygen species inhibitor/scavenger, could achieve its focal cerebral ischemia/reperfusion injury protective effect by modulating enzyme systems related to reactive oxygen species production or metabolism, including NADPH oxidase, myeloperoxidase, cyclooxygenase, and GSH peroxidase in neutrophils.