Analgecine regulates microglia polarization in ischemic stroke by inhibiting NF-κB through the TLR4 MyD88 pathway.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
    • Subject Terms:
      Infarction, Middle Cerebral Artery/*drug therapy ; Microglia/*chemistry ; Myeloid Differentiation Factor 88/*metabolism ; Toll-Like Receptor 4/*metabolism; Animals ; Brain Ischemia/metabolism ; Cytokines/chemistry ; Humans ; I-kappa B Proteins/metabolism ; Ischemic Stroke/metabolism ; Male ; NF-kappa B/metabolism ; Neurons/metabolism ; Neuroprotective Agents ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stroke/metabolism ; Toll-Like Receptors ; Transcription Factor RelA/metabolism
    • Abstract:
      Therapeutic strategies used to attenuate inflammation and to increase recovery of neurons after a stroke include microglia anti-inflammatory (M2) polarization and repression of proinflammatory (M1). Extracts isolated from Vaccina variola-inoculated rabbit skin, for example analgecine (AGC), have been used as a therapy for patients experiencing lower back pain associated with degenerative diseases of the spine for about twenty years. In the study presented here, neuroprotective effect associated with AGC was analyzed as well as the anti-inflammatory mechanism linked to AGC in terms of attenuating microglia-mediated neuronal damage. Rats were intravenously injected with AGC after middle cerebral artery occlusion (MCAO), which showed to suppress neuronal loss and reduce neurological deficits. In addition, AGC inhibited pro-inflammatory cytokine release and increased anti-inflammatory cytokines. Furthermore, this study revealed that treatment with AGC supported microglia transition from M1 to M2 in both oxygen-glucose deprivation/reperfusion (OGD/R) and LPS/IFN-γ induced microglia cells, as well as indirectly inhibited LPS/IFN-γ-induced neuronal damage through the modulation of microglial polarization. It is also important to note that AGC inhibited NF-κB p65 phosphorylation through repressing TLR4/Myd88/TRAF6 signaling pathway. In addition, we found that TLR4 inhibition by AGC depended on Myd88. Altogether, this work supports that AGC inhibits M1 microglial polarization and promotes anti-inflammation independently and dependently on TLR4/MyD88. Since it is shown to have neuroprotective effects in this study, AGC has great potential to be used in the clinic to reduce inflammation and aid in recovery after stroke.
      (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Analgecine; Cerebral ischemia; Inflammation; Microglial polarization; MyD88; TLR4
    • Accession Number:
      0 (Cytokines)
      0 (I-kappa B Proteins)
      0 (Myeloid Differentiation Factor 88)
      0 (NF-kappa B)
      0 (Neuroprotective Agents)
      0 (Toll-Like Receptor 4)
      0 (Toll-Like Receptors)
      0 (Transcription Factor RelA)
    • Publication Date:
      Date Created: 20210706 Date Completed: 20220124 Latest Revision: 20220124
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.intimp.2021.107930
    • Accession Number:
      34229178