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題名 Magnolia Polyphenols Attenuate Oxidative and Inflammatory Responses in Neurons and Microglial Cells
作者 詹銘煥
Chuang,Dennis Y;Chan,Ming-Huan;Zong,Yijia;Sheng,Wenwen;He,Yan;Jiang,Jing Hua;Simonyi,Agnes;Gu,Zezong;Fritsche,Kevin L;Cui, Jiankun;Lee,James C;Folk, William R;Lubahn,Dennis B;Sun,Albert Y;Sun,Grace Y
貢獻者 神科所
關鍵詞 ERK1/2; Honokiol; IFNγ; iNOS/NO; Inflammatory; Magnolol; Microglial cells; Oxidative; NADPH oxidase;Neurons
日期 2013.01
上傳時間 3-Dec-2013 18:19:54 (UTC+8)
摘要 Background: 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. Methods: 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. Results: 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. Conclusion: 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.
關聯 Journal of Neuroinflammation, 10(1), 1-14
資料類型 article
DOI http://dx.doi.org/10.1186/1742-2094-10-15
dc.contributor 神科所en_US
dc.creator (作者) 詹銘煥zh_TW
dc.creator (作者) Chuang,Dennis Y;Chan,Ming-Huan;Zong,Yijia;Sheng,Wenwen;He,Yan;Jiang,Jing Hua;Simonyi,Agnes;Gu,Zezong;Fritsche,Kevin L;Cui, Jiankun;Lee,James C;Folk, William R;Lubahn,Dennis B;Sun,Albert Y;Sun,Grace Yen_US
dc.date (日期) 2013.01en_US
dc.date.accessioned 3-Dec-2013 18:19:54 (UTC+8)-
dc.date.available 3-Dec-2013 18:19:54 (UTC+8)-
dc.date.issued (上傳時間) 3-Dec-2013 18:19:54 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/62101-
dc.description.abstract (摘要) Background: 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. Methods: 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. Results: 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. Conclusion: 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.-
dc.format.extent 770369 bytes-
dc.format.mimetype application/pdf-
dc.language.iso en_US-
dc.relation (關聯) Journal of Neuroinflammation, 10(1), 1-14en_US
dc.subject (關鍵詞) ERK1/2; Honokiol; IFNγ; iNOS/NO; Inflammatory; Magnolol; Microglial cells; Oxidative; NADPH oxidase;Neuronsen_US
dc.title (題名) Magnolia Polyphenols Attenuate Oxidative and Inflammatory Responses in Neurons and Microglial Cellsen_US
dc.type (資料類型) articleen
dc.identifier.doi (DOI) 10.1186/1742-2094-10-15en_US
dc.doi.uri (DOI) http://dx.doi.org/10.1186/1742-2094-10-15en_US