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β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke

Chronic treatment involving opioids exacerbates both the risk and severity of ischemic stroke. We have provided experimental evidence showing the anti-inflammatory and neuroprotective effects of the μ opioid receptor antagonist β-funaltrexamine for neurodegenerative diseases in rat neuron/glia cultu...

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Autores principales: Wu, Chih-Cheng, Chang, Cheng-Yi, Shih, Kuei-Chung, Hung, Chih-Jen, Wang, Ya-Yu, Lin, Shih-Yi, Chen, Wen-Ying, Kuan, Yu-Hsiang, Liao, Su-Lan, Wang, Wen-Yi, Chen, Chun-Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313048/
https://www.ncbi.nlm.nih.gov/pubmed/32485857
http://dx.doi.org/10.3390/ijms21113866
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author Wu, Chih-Cheng
Chang, Cheng-Yi
Shih, Kuei-Chung
Hung, Chih-Jen
Wang, Ya-Yu
Lin, Shih-Yi
Chen, Wen-Ying
Kuan, Yu-Hsiang
Liao, Su-Lan
Wang, Wen-Yi
Chen, Chun-Jung
author_facet Wu, Chih-Cheng
Chang, Cheng-Yi
Shih, Kuei-Chung
Hung, Chih-Jen
Wang, Ya-Yu
Lin, Shih-Yi
Chen, Wen-Ying
Kuan, Yu-Hsiang
Liao, Su-Lan
Wang, Wen-Yi
Chen, Chun-Jung
author_sort Wu, Chih-Cheng
collection PubMed
description Chronic treatment involving opioids exacerbates both the risk and severity of ischemic stroke. We have provided experimental evidence showing the anti-inflammatory and neuroprotective effects of the μ opioid receptor antagonist β-funaltrexamine for neurodegenerative diseases in rat neuron/glia cultures and a rat model of cerebral Ischemia/Reperfusion (I/R) injury. Independent of in vitro Lipopolysaccharide (LPS)/interferon (IFN-γ)-stimulated neuron/glia cultures and in vivo cerebral I/R injury in Sprague–Dawley rats, β-funaltrexamine downregulated neuroinflammation and ameliorated neuronal degeneration. Alterations in microglia polarization favoring the classical activation state occurred in LPS/IFN-γ-stimulated neuron/glia cultures and cerebral I/R-injured cortical brains. β-funaltrexamine shifted the polarization of microglia towards the anti-inflammatory phenotype, as evidenced by decreased nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2, along with increased CD163 and arginase 1. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by β-funaltrexamine was accompanied by the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein, along with signal transducers and activators of transcription transcriptional activities and associated upstream activators. The effects of β-funaltrexamine are closely linked with its action on neuroinflammation by switching microglia polarization from pro-inflammatory towards anti-inflammatory phenotypes. These findings provide new insights into the anti-inflammatory and neuroprotective mechanisms of β-funaltrexamine in combating neurodegenerative diseases, such as stroke.
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spelling pubmed-73130482020-06-29 β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke Wu, Chih-Cheng Chang, Cheng-Yi Shih, Kuei-Chung Hung, Chih-Jen Wang, Ya-Yu Lin, Shih-Yi Chen, Wen-Ying Kuan, Yu-Hsiang Liao, Su-Lan Wang, Wen-Yi Chen, Chun-Jung Int J Mol Sci Article Chronic treatment involving opioids exacerbates both the risk and severity of ischemic stroke. We have provided experimental evidence showing the anti-inflammatory and neuroprotective effects of the μ opioid receptor antagonist β-funaltrexamine for neurodegenerative diseases in rat neuron/glia cultures and a rat model of cerebral Ischemia/Reperfusion (I/R) injury. Independent of in vitro Lipopolysaccharide (LPS)/interferon (IFN-γ)-stimulated neuron/glia cultures and in vivo cerebral I/R injury in Sprague–Dawley rats, β-funaltrexamine downregulated neuroinflammation and ameliorated neuronal degeneration. Alterations in microglia polarization favoring the classical activation state occurred in LPS/IFN-γ-stimulated neuron/glia cultures and cerebral I/R-injured cortical brains. β-funaltrexamine shifted the polarization of microglia towards the anti-inflammatory phenotype, as evidenced by decreased nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2, along with increased CD163 and arginase 1. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by β-funaltrexamine was accompanied by the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein, along with signal transducers and activators of transcription transcriptional activities and associated upstream activators. The effects of β-funaltrexamine are closely linked with its action on neuroinflammation by switching microglia polarization from pro-inflammatory towards anti-inflammatory phenotypes. These findings provide new insights into the anti-inflammatory and neuroprotective mechanisms of β-funaltrexamine in combating neurodegenerative diseases, such as stroke. MDPI 2020-05-29 /pmc/articles/PMC7313048/ /pubmed/32485857 http://dx.doi.org/10.3390/ijms21113866 Text en © 2020 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
Wu, Chih-Cheng
Chang, Cheng-Yi
Shih, Kuei-Chung
Hung, Chih-Jen
Wang, Ya-Yu
Lin, Shih-Yi
Chen, Wen-Ying
Kuan, Yu-Hsiang
Liao, Su-Lan
Wang, Wen-Yi
Chen, Chun-Jung
β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
title β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
title_full β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
title_fullStr β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
title_full_unstemmed β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
title_short β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
title_sort β-funaltrexamine displayed anti-inflammatory and neuroprotective effects in cells and rat model of stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313048/
https://www.ncbi.nlm.nih.gov/pubmed/32485857
http://dx.doi.org/10.3390/ijms21113866
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