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

doi:10.3390/ijms21113866

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24842

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24842

Title:	beta-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
Authors:	Wu, CC;Chang, CY;Shih, KC;Hung, CJ;Wang, YY;Lin, SY;Chen, WY;Kuan, YH;Liao, SL;Wang, WY;Chen, CJ
Keywords:	microglia polarization;neuroinflammation;opioid;stroke
Date:	2020
Issue Date:	2022-08-09T08:08:52Z (UTC)
Publisher:	MDPI
Abstract:	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 mu opioid receptor antagonist beta-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-gamma)-stimulated neuron/glia cultures and in vivo cerebral I/R injury in Sprague-Dawley rats, beta-funaltrexamine downregulated neuroinflammation and ameliorated neuronal degeneration. Alterations in microglia polarization favoring the classical activation state occurred in LPS/IFN-gamma-stimulated neuron/glia cultures and cerebral I/R-injured cortical brains. beta-funaltrexamine shifted the polarization of microglia towards the anti-inflammatory phenotype, as evidenced by decreased nitric oxide, tumor necrosis factor-alpha, interleukin-1 beta, and prostaglandin E2, along with increased CD163 and arginase 1. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by beta-funaltrexamine was accompanied by the reduction of NF-kappa B, 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 beta-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 beta-funaltrexamine in combating neurodegenerative diseases, such as stroke.
URI:	http://dx.doi.org/10.3390/ijms21113866 https://www.webofscience.com/wos/woscc/full-record/WOS:000543400300128 https://ir.csmu.edu.tw:8080/handle/310902500/24842
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2020 ,v21 ,issue 11
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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