Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells.
Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells.
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DOI：
10.1186/1742-2094-10-15
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发表时间：
2013-01-29
影响因子：
9.3
通讯作者：
Sun GY
中科院分区：
文献类型：
--
作者：
Chuang DY;Chan MH;Zong Y;Sheng W;He Y;Jiang JH;Simonyi A;Gu Z;Fritsche KL;Cui J;Lee JC;Folk WR;Lubahn DB;Sun AY;Sun GY
在东方医学中，杜仲的树皮被用来治疗各种各样的药物，包括一些神经系统疾病。厚朴酚（Magnolol，Mag）和和厚朴酚（Honokalin，Hon）是厚朴中多酚类化合物的异构体，具有抗氧化、抗炎和神经保护作用。在这项研究中，我们调查这些异构体的能力，以抑制氧化应激的神经元刺激的离子型谷氨酸受体激动剂N-甲基-D-天冬氨酸（NMDA）和氧化和炎症反应的小胶质细胞激活的干扰素-γ（IFNγ）和脂多糖（LPS）。我们还试图阐明的机制和参与的信号通路，在小胶质细胞中的活性氧（ROS）的生产，苦参碱诱导。二氢乙锭（DHE）用于测定神经元中的超氧化物产生，而CM-H2 DCF-DA用于测试小鼠（BV-2）和大鼠（HAPI）永生化小胶质细胞中的ROS产生。NADPH氧化酶抑制剂（例如，二苯基碘铵（DPI），AEBSF和夹竹桃素）和免疫细胞化学靶向p47 phox和gp 91 phox被用来评估NADPH氧化酶的参与。Western blotting检测iNOS和ERK 1/2表达，Griess反应检测NO浓度。将Hon和Mag（1-10 μM）暴露于神经元24 h不会改变神经元的活力，但两种化合物（10 μM）均抑制NMDA刺激的超氧化物生成，这是一种已知涉及NADPH氧化酶的途径。在小胶质细胞中，Hon和Mag抑制IFNγ± LPS诱导的iNOS表达、NO和ROS产生。抑制剂和免疫细胞化学研究进一步证实了IFNγ通过p-ERK依赖性途径激活NADPH氧化酶的重要作用。Hon和Mag在较小程度上抑制IFNγ诱导的p-ERK 1/2及其下游ROS和NO产生途径。本研究强调了NADPH氧化酶在神经元和小胶质细胞中介导氧化应激的重要作用，并揭示了IFNγ在刺激MAPK/ERK 1/2信号通路以激活小胶质细胞中NADPH氧化酶中的作用。Hon和Mag至少部分通过抑制IFNγ诱导的p-ERK 1/2及其下游途径提供抗氧化或抗炎作用。
The bark of magnolia has been used in Oriental medicine to treat a variety of remedies, including some neurological disorders. Magnolol (Mag) and honokiol (Hon) are isomers of polyphenolic compounds from the bark of Magnolia officinalis, and have been identified as major active components exhibiting anti-oxidative, anti-inflammatory, and neuroprotective effects. In this study, we investigate the ability of these isomers to suppress oxidative stress in neurons stimulated by the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) and oxidative and inflammatory responses in microglial cells activated by interferon-γ (IFNγ) and lipopolysaccharide (LPS). We also attempt to elucidate the mechanism and signaling pathways involved in cytokine-induced production of reactive oxygen species (ROS) in microglial cells. Dihydroethidium (DHE) was used to assay superoxide production in neurons, while CM-H2DCF-DA was used to test for ROS production in murine (BV-2) and rat (HAPI) immortalized microglial cells. NADPH oxidase inhibitors (for example, diphenyleneiodonium (DPI), AEBSF, and apocynin) and immunocytochemistry targeting p47phox and gp91phox were used to assess the involvement of NADPH oxidase. Western blotting was used to assess iNOS and ERK1/2 expression, and the Griess reaction protocol was employed to determine nitric oxide (NO) concentration. Exposure of Hon and Mag (1–10 μM) to neurons for 24 h did not alter neuronal viability, but both compounds (10 μM) inhibited NMDA-stimulated superoxide production, a pathway known to involve NADPH oxidase. In microglial cells, Hon and Mag inhibited IFNγ±LPS-induced iNOS expression, NO, and ROS production. Studies with inhibitors and immunocytochemical assay further demonstrated the important role of IFNγ activating the NADPH oxidase through the p-ERK-dependent pathway. Hon and, to a lesser extent, Mag inhibited IFNγ-induced p-ERK1/2 and its downstream pathway for ROS and NO production. This study highlights the important role of NADPH oxidase in mediating oxidative stress in neurons and microglial cells and has unveiled the role of IFNγ in stimulating the MAPK/ERK1/2 signaling pathway for activation of NADPH oxidase in microglial cells. Hon and Mag offer anti-oxidative or anti-inflammatory effects, at least in part, through suppressing IFNγ-induced p-ERK1/2 and its downstream pathway.
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影响因子：
5
作者：
Liou, KT;Shen, YC;Tsai, SK
通讯作者：
Tsai, SK
影响因子：
5.5
作者：
Casbon, Amy-Jo;Long, Matthew E.;Dinauer, Mary C.
通讯作者：
Dinauer, Mary C.
影响因子：
5.4
作者：
Jung, Hyo-Won;Seo, Un-Kyo;Park, Yong-Ki
通讯作者：
Park, Yong-Ki
影响因子：
5.6
作者：
Kao, Tsung-Kuei;Ou, Yen-Chuan;Chen, Chun-Jung
通讯作者：
Chen, Chun-Jung
影响因子：
6.1
作者：
Kuo, Daih-Huang;Lai, You-Syuan;Pan, Min-Hsiung
通讯作者：
Pan, Min-Hsiung