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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2013

Open Access 01-12-2013 | Research

Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells

Authors: Dennis Y Chuang, Ming-Huan Chan, Yijia Zong, Wenwen Sheng, Yan He, Jing Hua Jiang, Agnes Simonyi, Zezong Gu, Kevin L Fritsche, Jiankun Cui, James C Lee, William R Folk, Dennis B Lubahn, Albert Y Sun, Grace Y Sun

Published in: Journal of Neuroinflammation | Issue 1/2013

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Abstract

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.
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Metadata
Title
Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells
Authors
Dennis Y Chuang
Ming-Huan Chan
Yijia Zong
Wenwen Sheng
Yan He
Jing Hua Jiang
Agnes Simonyi
Zezong Gu
Kevin L Fritsche
Jiankun Cui
James C Lee
William R Folk
Dennis B Lubahn
Albert Y Sun
Grace Y Sun
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-10-15

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