2. Academic Validation
  3. β-Funaltrexamine Displayed Anti-inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke

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

  • Int J Mol Sci. 2020 May 29;21(11):3866. doi: 10.3390/ijms21113866.
Chih-Cheng Wu 1 2 3,  Cheng-Yi Chang 4,  Kuei-Chung Shih 5,  Chih-Jen Hung 1,  Ya-Yu Wang 6 7,  Shih-Yi Lin 7 8,  Wen-Ying Chen 9,  Yu-Hsiang Kuan 10,  Su-Lan Liao 11,  Wen-Yi Wang 12,  Chun-Jung Chen 11 13
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 2 Department of Financial Engineering, Providence University, Taichung City 433, Taiwan.
  • 3 Department of Data Science and Big Data Analytics, Providence University, Taichung City 433, Taiwan.
  • 4 Department of Surgery, Feng Yuan Hospital, Taichung City 420, Taiwan.
  • 5 Department of Computer Science and Information Management, Providence University, Taichung City 433, Taiwan.
  • 6 Department of Family Medicine, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 7 Institute of Clinical Medicine, National Yang Ming University, Taipei City 112, Taiwan.
  • 8 Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 9 Department of Veterinary Medicine, National Chung-Hsing University, Taichung City 402, Taiwan.
  • 10 Department of Pharmacology, Chung Shan Medical University, Taichung City 402, Taiwan.
  • 11 Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 12 Department of Nursing, Hung Kuang University, Taichung City 433, Taiwan.
  • 13 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 404, Taiwan.
PMID: 32485857 DOI: 10.3390/ijms21113866
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 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.

Keywords

microglia polarization; neuroinflammation; opioid; stroke.

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