Targeting of neuroinflammation by glibenclamide in Covid-19: old weapon from arsenal

Inflammopharmacology. 2023 Feb;31(1):1-7. doi: 10.1007/s10787-022-01087-8. Epub 2022 Nov 23.

Abstract

In coronavirus disease 2019 (Covid-19) era, neuroinflammation may develop due to neuronal tropism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or associated immune activation, cytokine storm, and psychological stress. SARS-CoV-2 infection and linked cytokine storm may cause blood-brain barrier (BBB) injury through which activated immune cells and SARS-CoV-2 can pass into the brain causing activation of glial cells with subsequent neuroinflammation. Different therapeutic regimens were suggested to alleviate Covid-19-induced neuroinflammation. Since glibenclamide has anti-inflammatory and neuroprotective effects, it could be effective in mitigation of SARS-CoV-2 infection-induced neuroinflammation. Glibenclamide is a second-generation drug from the sulfonylurea family, which acts by inhibiting the adenosine triphosphate (ATP)-sensitive K channel in the regulatory subunit of type 1 sulfonylurea receptor (SUR-1) in pancreatic β cells. Glibenclamide reduces neuroinflammation and associated BBB injury by inhibiting the nod-like receptor pyrin 3 (NLRP3) inflammasome, oxidative stress, and microglial activation. Therefore, glibenclamide through inhibition of NLRP3 inflammasome, microglial activation, and oxidative stress may attenuate SARS-CoV-2-mediated neuroinflammation.

Keywords: Covid-19; Glibenclamide; Neuroinflammation.

Publication types

  • Review

MeSH terms

  • COVID-19*
  • Cytokine Release Syndrome
  • Glyburide / pharmacology
  • Humans
  • Inflammasomes*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Neuroinflammatory Diseases
  • SARS-CoV-2

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Glyburide