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Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats

Parkinson’s disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could dama...

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Autores principales: Chen, Guangxin, Liu, Juxiong, Jiang, Liqiang, Ran, Xin, He, Dewei, Li, Yuhang, Huang, Bingxu, Wang, Wei, Fu, Shoupeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795964/
https://www.ncbi.nlm.nih.gov/pubmed/29267220
http://dx.doi.org/10.3390/ijms19010012
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author Chen, Guangxin
Liu, Juxiong
Jiang, Liqiang
Ran, Xin
He, Dewei
Li, Yuhang
Huang, Bingxu
Wang, Wei
Fu, Shoupeng
author_facet Chen, Guangxin
Liu, Juxiong
Jiang, Liqiang
Ran, Xin
He, Dewei
Li, Yuhang
Huang, Bingxu
Wang, Wei
Fu, Shoupeng
author_sort Chen, Guangxin
collection PubMed
description Parkinson’s disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could damage DA neurons. Hence, the inhibition of microglial activation may provide a new approach for treating PD. Galangin has been shown to inhibit inflammation in a variety of diseases, but not PD. In this study, we aimed to investigate the anti-inflammatory effect of galangin and the underlying mechanisms in Lipopolysaccharide (LPS) induced PD models. We first examined the protective effect of galangin in the LPS-induced PD rat model. Specifically, we investigated the effects on motor dysfunction, microglial activation, and the loss of DA neurons. Then, galangin was used to detect the impact on the inflammatory responses and inflammatory signaling pathways in LPS-induced BV-2 cells. The in vivo results showed that galangin dose-dependently attenuates the activation of microglia, the loss of DA neurons, and motor dysfunction. In vitro, galangin markedly inhibited LPS-induced expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase 2 (COX-2), and induced nitric oxide synthase (iNOS) via associating with the phosphorylation of c-JUN N-terminal Kinase (JNK), p38, protein kinase B (AKT), and nuclear factor κB (NF-κB) p65. Collectively, the results indicated that galangin has a role in protecting DA neurons by inhibiting microglial activation.
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spelling pubmed-57959642018-02-09 Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats Chen, Guangxin Liu, Juxiong Jiang, Liqiang Ran, Xin He, Dewei Li, Yuhang Huang, Bingxu Wang, Wei Fu, Shoupeng Int J Mol Sci Article Parkinson’s disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could damage DA neurons. Hence, the inhibition of microglial activation may provide a new approach for treating PD. Galangin has been shown to inhibit inflammation in a variety of diseases, but not PD. In this study, we aimed to investigate the anti-inflammatory effect of galangin and the underlying mechanisms in Lipopolysaccharide (LPS) induced PD models. We first examined the protective effect of galangin in the LPS-induced PD rat model. Specifically, we investigated the effects on motor dysfunction, microglial activation, and the loss of DA neurons. Then, galangin was used to detect the impact on the inflammatory responses and inflammatory signaling pathways in LPS-induced BV-2 cells. The in vivo results showed that galangin dose-dependently attenuates the activation of microglia, the loss of DA neurons, and motor dysfunction. In vitro, galangin markedly inhibited LPS-induced expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase 2 (COX-2), and induced nitric oxide synthase (iNOS) via associating with the phosphorylation of c-JUN N-terminal Kinase (JNK), p38, protein kinase B (AKT), and nuclear factor κB (NF-κB) p65. Collectively, the results indicated that galangin has a role in protecting DA neurons by inhibiting microglial activation. MDPI 2017-12-21 /pmc/articles/PMC5795964/ /pubmed/29267220 http://dx.doi.org/10.3390/ijms19010012 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Guangxin
Liu, Juxiong
Jiang, Liqiang
Ran, Xin
He, Dewei
Li, Yuhang
Huang, Bingxu
Wang, Wei
Fu, Shoupeng
Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats
title Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats
title_full Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats
title_fullStr Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats
title_full_unstemmed Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats
title_short Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson’s Disease in Rats
title_sort galangin reduces the loss of dopaminergic neurons in an lps-evoked model of parkinson’s disease in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795964/
https://www.ncbi.nlm.nih.gov/pubmed/29267220
http://dx.doi.org/10.3390/ijms19010012
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